tag:theconversation.com,2011:/uk/topics/drug-delivery-420/articlesDrug delivery – The Conversation2023-11-14T13:25:49Ztag:theconversation.com,2011:article/2167872023-11-14T13:25:49Z2023-11-14T13:25:49ZInsulin injections could one day be replaced with rock music − new research in mice<figure><img src="https://images.theconversation.com/files/558688/original/file-20231109-21-ic46x7.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2120%2C1414&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Turns out pop songs and movie soundtracks are key to a new system to deliver insulin.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cheering-audience-at-music-concert-royalty-free-image/1384296998">Sammyvision/Moment via Getty Images</a></span></figcaption></figure><p>More than <a href="https://www.cdc.gov/diabetes/basics/diabetes.html">37 million people</a> in the U.S. have diabetes. According to the American Diabetes Association, <a href="https://www2.diabetes.org/newsroom/press-releases/2022/american-diabetes-association-announces-support-for-insulin-act-at-senate-press-conference">8.4 million Americans</a> needed to take insulin in 2022 to lower their blood sugar. Insulin, however, is <a href="https://doi.org/10.1111/jphp.12852">tricky to deliver</a> into the body orally because it is a protein easily <a href="https://theconversation.com/many-drugs-cant-withstand-stomach-acid-a-new-delivery-method-could-lead-to-more-convenient-medications-183421">destroyed in the stomach</a>.</p>
<p>While researchers are developing <a href="https://www.acs.org/pressroom/presspacs/2023/january/another-step-toward-an-insulin-tablet.html">pills that resist digestion</a> in the stomach and <a href="https://samueli.ucla.edu/smart-insulin-patch/">skin patches</a> that monitor blood sugar and automatically release insulin, the most reliable way currently to take insulin is through frequent injections.</p>
<p>I am a professor of <a href="https://medicine.iu.edu/faculty/13502/sullivan-william">pharmacology and toxicology</a> at Indiana University School of Medicine, where my colleagues and I study drug delivery systems. Researching innovative new ways to get medications into the body can improve how well patients respond to and comply with treatments. An easier way to take insulin would be music to the ears of many people with diabetes, especially those who aren’t fans of needles.</p>
<p>In a recent study in <a href="https://doi.org/10.1016/S2213-8587(23)00153-5">The Lancet Diabetes & Endocrinology</a>, researchers engineered cells to release insulin in response to specific sound waves: the music of the band Queen. Though it still has a long way to go, this new system may one day replace the insulin injection with a dose of rock ’n’ roll.</p>
<h2>What is diabetes?</h2>
<p><a href="https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-20371444">Diabetes is a chronic disease</a> that arises when the body fails to make enough insulin or respond to insulin. <a href="https://my.clevelandclinic.org/health/articles/22601-insulin">Insulin is a hormone</a> the pancreas makes in response to the rise in sugar concentration in the blood when the body digests food. This crucial hormone gets those sugars out of the blood and into muscles and tissues where it is used or stored for energy.</p>
<p>Without insulin, <a href="https://www.mayoclinic.org/diseases-conditions/hyperglycemia/symptoms-causes/syc-20373631">blood sugar levels remain high</a> and cause symptoms that include frequent urination, thirst, blurry vision and fatigue. Left untreated, this hyperglycemia can be life-threatening, causing organ damage and a diabetic coma. According to the U.S. Centers for Disease Control and Prevention, diabetes is the <a href="https://www.cdc.gov/diabetes/basics/diabetes.html">No. 1 cause</a> of kidney failure, lower-limb amputations and adult blindness, making it the eighth most common cause of death in the U.S.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Q6rLXPJ6j_I?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Diabetes results when the body either doesn’t produce enough insulin or is no longer responsive to it.</span></figcaption>
</figure>
<p>Treating diabetes is straightforward: When the body is lacking insulin, give it more insulin. Scientists have <a href="https://www.vox.com/2019/4/3/18293950/why-is-insulin-so-expensive">mastered how to make the hormone</a>, but direct injection is the only effective way to get it into the body. Diabetic patients usually have to carry insulin vials and needles wherever they go. Considering that <a href="https://theconversation.com/over-half-of-adults-unvaccinated-for-covid-19-fear-needles-heres-whats-proven-to-help-161636">many people fear needles</a>, this may not be an ideal way to manage the disease.</p>
<p>This challenge has sparked researchers to look into new ways to deliver insulin more easily.</p>
<h2>What is cellular engineering?</h2>
<p>Cells are the basic unit of life. Your body is composed of <a href="https://pubmed.ncbi.nlm.nih.gov/35832316/">hundreds of different types of cells</a> that carry out specialized functions. In some diabetic patients, the pancreatic beta cells that make insulin have malfunctioned or died. What if there were a way to replace these defective cells with new ones that could produce insulin on demand?</p>
<p>That’s where cellular engineering comes in. <a href="https://doi.org/10.1126/science.adf8627">Cellular engineering</a> involves genetically modifying a cell to perform a specific function, like producing insulin. <a href="https://medlineplus.gov/genetics/gene/ins/">Installing the gene that makes insulin</a> into cells is not difficult, but controlling when the cell makes it has been a challenge. Insulin should be made only in response to high blood sugar levels following a meal, not at any other time.</p>
<p>Scientists have been exploring the idea of using <a href="https://www.britannica.com/science/ion-channel">ion channels</a> – proteins embedded in a cell’s membrane that regulate the flow of ions such as calcium or chloride – like a remote-controlled device to activate cellular activity. Cells with specific types of ion channel in their membranes can be <a href="https://doi.org/10.1126/science.abb9122">activated in response to certain stimuli</a>, such as light, electricity, magnetic fields or mechanical stimulation. Such ion channels exist naturally as sensory devices to help cells and organisms respond to light, magnetism, touch or sound. For example, <a href="https://doi.org/10.1016/j.neuron.2018.07.033">hair cells in the inner ear</a> have mechanosensitive ion channels that respond to sound waves. </p>
<h2>Combining cellular engineering with Queen</h2>
<p>Bioengineering professor <a href="https://scholar.google.com/citations?user=Re5ypoQAAAAJ&hl=en">Martin Fussenegger</a> of ETH Zurich, a university in Basel, Switzerland, led a recent study that used a mechanosensitive ion channel as a remote control to signal cells to <a href="https://doi.org/10.1016/S2213-8587(23)00153-5">make insulin in response to specific sound waves</a>.</p>
<p>These “MUSIC-controlled, insulin-releasing cells” – MUSIC is short for music-inducible cellular control – were cultured in the lab next to loudspeakers. His team tested a variety of musical genres of different intensities and speeds.</p>
<p>Among the songs they played were pop songs like Michael Jackson’s “Billie Jean,” Queen’s “We Will Rock You” and the Eagles’ “Hotel California”; classical pieces such as Beethoven’s “Für Elise” and Mozart’s “Alla Turca”; and movie themes such as Soundgarden’s “Live To Rise,” which was featured in “The Avengers,” a Marvel film. They found that pop music heavy in low bass and movie soundtracks were better able to trigger insulin release compared with classical music, and cells were able to release insulin within minutes of exposure to the song.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of person injecting insulin into upper arm" src="https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/558690/original/file-20231109-27-tjh26u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Many people with diabetes have to take frequent insulin injections to control their blood sugar levels.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/taking-an-insulin-shot-at-home-royalty-free-image/1426368585">Caíque de Abreu/E+ via Getty Images</a></span>
</figcaption>
</figure>
<p>In particular, they found that the Queen song “<a href="https://www.youtube.com/watch?v=-tJYN-eG1zk">We Will Rock You</a>” most faithfully mimicked the rate of insulin release in normal pancreatic beta cells.</p>
<p>The team then implanted the MUSIC-controlled, insulin-releasing cells into diabetic mice. Listening to the Queen song for 15 minutes once a day returned the amount of insulin in their blood to normal levels. Blood sugar levels returned to normal as well. In contrast, mice that were not exposed to the song remained hyperglycemic.</p>
<h2>Could music make insulin in people?</h2>
<p>Despite these promising results, much more research is needed before this musical approach to producing insulin can be considered for human use.</p>
<p>One concern is the possibility of making too much insulin, which can also cause <a href="https://www.mayoclinic.org/diseases-conditions/hypoglycemia/symptoms-causes/syc-20373685">health problems</a>. Fussenegger’s study found that talking and background noise such as the racket made by airplanes, lawn mowers or firetrucks did not trigger the insulin production system in mice. The music also needed to be played close to the abdomen where the MUSIC-controlled, insulin-releasing cells were implanted.</p>
<p>In an email, Fussenegger explained that extensive clinical trials must be performed to ensure efficacy and safety of the technique and to determine how long the cellular implants can last. As with introducing any foreign material into the body, <a href="https://medlineplus.gov/ency/article/000815.htm">tissue rejection</a> is also a concern.</p>
<p>Cellular engineering may one day provide a much-needed alternative to frequent injections of insulin for the millions of people with diabetes around the world. In the future, different cell types could be engineered to release other drugs in the body more conveniently.</p><img src="https://counter.theconversation.com/content/216787/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bill Sullivan receives funding from the National Institutes of Health.</span></em></p>Researchers successfully treated diabetes in mice by engineering cells to make insulin in response to the music of Queen.Bill Sullivan, Professor of Pharmacology & Toxicology, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1902252022-12-18T13:16:47Z2022-12-18T13:16:47ZLong-acting injectable PrEP is a big step forward in HIV prevention<figure><img src="https://images.theconversation.com/files/501164/original/file-20221214-16278-cj9xs2.jpg?ixlib=rb-1.1.0&rect=66%2C473%2C6908%2C4429&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The HIV prevention drug cabotegravir, which is delivery by injection every eight weeks, is not yet available in Canada.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>One year ago, <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-injectable-treatment-hiv-pre-exposure-prevention">the United States approved a new injectable drug that prevents HIV</a>. </p>
<p><a href="https://doi.org/10.1056/NEJMoa2101016">After successful clinical trials</a>, long-acting cabotegravir was found to be almost 100 per cent effective at preventing HIV. It was approved in the U.S. on Dec. 20, 2021, for use as HIV pre-exposure prophylaxis (PrEP). This approval means that eligible individuals can now receive this medication every eight weeks to prevent sexually-acquired HIV infection.</p>
<p>However this new drug, which would help address some of the <a href="https://www.cdc.gov/nchhstp/newsroom/fact-sheets/hiv/state-of-the-hiv-epidemic-factsheet.html#gains-challenges">ongoing challenges with HIV prevention</a> for those who remain at high risk, is still not available in Canada.</p>
<h2>HIV in Canada</h2>
<p>The number of new HIV infections has not changed much over the past couple of decades and <a href="https://www.canada.ca/en/public-health/services/publications/diseases-conditions/summary-estimates-hiv-incidence-prevalence-canadas-progress-90-90-90.html">approximately 13 per cent of people living with HIV in Canada are undiagnosed</a>. This demonstrates the need for more HIV prevention strategies. </p>
<p>While long-acting injectable PrEP is new, oral PrEP — <a href="https://www.catie.ca/pre-exposure-prophylaxis-prep-0">a pill taken either daily or around sexual activity</a> — was approved in the U.S. back in 2012. <a href="https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2017-43/ccdr-volume-43-12-december-7-2017/hiv-pre-exposure-prophylaxis-use-canada.html">Canada only approved oral PrEP in 2016</a>. And we are once again falling behind the U.S. on making injectable PrEP available here.</p>
<p><a href="https://doi.org/10.1503/cmaj.220645">Oral PrEP already reduces the risk of HIV by almost 100 per cent</a> when taken consistently, but recent clinical trials show that injectable PrEP is even more effective. The main advantage of injectable PrEP is that going for injections every two months is a lot easier to remember than taking pills every day, or taking pills before and after sexual activity. The switch from oral pills to injectable shots means that individuals can more easily maintain adherence, which impacts the overall effectiveness of PrEP as HIV prevention.</p>
<figure class="align-center ">
<img alt="Close-up of a hand with four blue caplets in the palm." src="https://images.theconversation.com/files/500660/original/file-20221213-4932-7g9lp5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/500660/original/file-20221213-4932-7g9lp5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=424&fit=crop&dpr=1 600w, https://images.theconversation.com/files/500660/original/file-20221213-4932-7g9lp5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=424&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/500660/original/file-20221213-4932-7g9lp5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=424&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/500660/original/file-20221213-4932-7g9lp5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=533&fit=crop&dpr=1 754w, https://images.theconversation.com/files/500660/original/file-20221213-4932-7g9lp5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=533&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/500660/original/file-20221213-4932-7g9lp5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=533&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Oral PrEP reduces the risk of HIV infection, but injectable PrEP would offer a long-acting option.</span>
<span class="attribution"><span class="source">(AP Photo/Jeff Chiu)</span></span>
</figcaption>
</figure>
<p>Although some people might prefer pills to shots for various reasons, injectable PrEP provides another option, and <a href="https://doi.org/10.1038/s41598-021-01634-3">people like having different HIV prevention options available to them</a>. At the individual level, injectables mean more choices. At the population level, more choices mean more prevention because different people might be willing to use different kinds of PrEP to suit their needs.</p>
<p>Contraception research has also demonstrated the importance of expanding people’s medication options. <a href="https://my.clevelandclinic.org/health/drugs/4086-depo-provera%C2%AE-birth-control-shot#:%7E:text=Commonly%20referred%20to%20as%20the,taken%20according%20to%20the%20schedule.">Injectable contraceptives</a> highlight how this technology improves both sexual and reproductive health.</p>
<p><a href="https://doi.org/10.1093/cid/cit085">Oral PrEP is often compared with the birth control pill</a>. There is a need to better understand how new injectable options for both contraception and HIV prevention affect adherence, access and the relationships of those who use them. </p>
<p>Both injectable and oral PrEP are safe and highly effective and they each have very few side-effects. Injectable PrEP has mild injection site reactions, including swelling, redness and pain.</p>
<p>There are also <a href="https://blog.catie.ca/2022/03/25/the-future-of-prep-is-now/">several other new HIV PrEP options</a> that are still being studied in clinical trials, including exciting long-acting oral, injectable, implantable and infusion options that are administered at different time intervals and could fit the different schedules and preferences of people interested in HIV prevention.</p>
<h2>Preparing for prevention</h2>
<p>We can be ready for these new developments by learning from our past experiences with the approval and implementation of previous HIV prevention strategies, like oral PrEP. Some individuals and communities still face barriers to PrEP, <a href="https://www.catie.ca/prevention-in-focus/overcoming-barriers-to-prep-program-models-using-diverse-settings-and-providers">like access to health-care providers who are knowledgeable about it</a>, and these barriers can perpetuate health inequalities.</p>
<p>Our research project, <a href="https://www.cbrc.net/futureofprep">The Future of PrEP is Now</a>, focuses specifically on community readiness for long-acting injectable PrEP because it has the potential to help overcome previous barriers to PrEP. Oral PrEP can still be inaccessible, expensive and stigmatized for many people in Canada and the one-pill-a-day adherence can be especially challenging. </p>
<p>Communities of Two-Spirit, gay, bisexual, queer and other men who have sex with men (2SGBQM) are <a href="https://www.catie.ca/the-epidemiology-of-hiv-in-canada">still disproportionately affected by HIV, and HIV rates are not declining in Canada</a>. 2SGBQM are also under-reached by existing PrEP programs, especially those who are Indigenous, Black, people of colour, rural, people who use substances, transgender and non-binary.</p>
<p>In our research, we talk to members of under-reached communities of 2SGBQM as well as the health-care providers who serve them to:</p>
<ol>
<li>learn their preferences regarding future long-acting injectable PrEP options</li>
<li>assess the feasibility of various models of delivering injectable PrEP </li>
<li>design a national study of injectable PrEP that responds to the needs and priorities of individuals already experiencing barriers to oral PrEP.</li>
</ol>
<p>In a recent public webinar, we asked <a href="https://www.catie.ca/prep-where-are-we-going">“where are we going?”</a> with PrEP as we plan for a long-acting injectable option to become available in Canada in the near future. We want to ensure that when this new treatment is approved, long-acting PrEP is quickly available and as equally accessible as oral PrEP to those who will benefit from it the most. Raising awareness and building support for this new HIV prevention strategy will help meet those goals.</p><img src="https://counter.theconversation.com/content/190225/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Montess receives funding from the Canadian Institutes of Health Research, Mitacs, the Social Sciences and Humanities Research Council, and the Michael Smith Foundation for Health Research. He is affiliated with the University of Victoria. </span></em></p><p class="fine-print"><em><span>Darrell Tan receives funding from the Canada Research Chairs program, the Canadian Institutes of Health Research, the CIHR Canadian HIV Trials Network, the Public Health Agency of Canada, the Canadian Foundation for AIDS Research, and the Ontario HIV Treatment Network. He is affiliated with St. Michael's Hospital and the University of Toronto. </span></em></p><p class="fine-print"><em><span>Nathan John Lachowsky receives funding from the Canadian Institutes of Health Research, Social Sciences and Humanities Research Council, MITACS, Public Health Agency of Canada, Canadian Blood Services, Canadian Foundation for AIDS Research, Michael Smith Health Research British Columbia, Government of British Columbia, Vancouver Foundation, and Victoria Foundation. He is affiliated with the Community Based Research Centre.</span></em></p>The next step in HIV prevention — long-acting injectable pre-exposure prophylaxis (PrEP) — is not yet available in Canada, a year after its approval in the U.S.Michael Montess, Postdoctoral Associate, Rotman Institute of Philosophy, Western UniversityDarrell Tan, Clinician-Scientist, St. Michael’s Hospital; Associate Professor, Faculty of Medicine, University of TorontoNathan John Lachowsky, Associate Professor, Public Health & Social Policy; Special Advisor Health Research, Office of the Vice-President Research and Innovation, University of VictoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1949062022-12-13T13:20:32Z2022-12-13T13:20:32ZTiming matters for medications – your circadian rhythm influences how well treatments work and how much they might harm you<figure><img src="https://images.theconversation.com/files/500478/original/file-20221212-110709-c1r8v2.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5100%2C3397&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Chronotherapeutic drug delivery aims to maximize treatment effectiveness and minimize side effects.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/clock-and-pills-and-tablets-around-it-royalty-free-illustration/1323067934">Vaselena/iStock via Getty Images Plus</a></span></figcaption></figure><p>All living organisms on Earth are exposed to a 24-hour day-night cycle. This cycle is the reason why people rest during the darkness of night and are active during the light of day. Consequently, all <a href="https://theconversation.com/your-body-has-an-internal-clock-that-dictates-when-you-eat-sleep-and-might-have-a-heart-attack-all-based-on-time-of-day-178601">human body functions</a> also follow this daily rhythm, and the timing of behaviors like exercise or food intake can significantly influence your health. For example, <a href="https://doi.org/10.3177/jnsv.68.S2">eating at night</a> can lead to weight gain over time because while daytime food intake is used for activities, food intake at night leads to increased fat storage because the body expects to be at rest.</p>
<p>When you take your medications is also influenced by your circadian rhythm. <a href="https://doi.org/10.1073/pnas.1408886111">Many drug targets</a> in the body follow a 24-hour cycle. This means that the specific proteins a drug is designed to modify can react differently to the medication over the course of a 24-hour time period. Because how the body responds to a medication can differ depending on whether it is taken during the day or at night, it logically follows that taking medications at specific times could help increase their effectiveness and reduce unwanted side effects.</p>
<p>When doctors prescribe medication for people, they <a href="https://doi.org/10.1126%2Fscience.aax7621">rarely consider</a> the best time to take it. There are two main reasons for that oversight. First, many physicians are not aware that some drugs work better during a specific time of the day. And second, most drugs have not been studied for possible different effects during a 24-hour cycle. As such, patients are directed to take most drugs during the morning or evening primarily to ensure compliance.</p>
<p><a href="https://medschool.cuanschutz.edu/anesthesiology/research-innovation/clinical-research/eckle-lab">My lab</a> <a href="https://scholar.google.com/citations?hl=en&user=QeAbWicAAAAJ&view_op=list_works&sortby=pubdate">and I</a> have been studying chronotherapy, or how time of day affects disease development and treatment effectiveness, for many years. In our <a href="https://doi.org/10.3389%2Ffcvm.2022.982209">recently published research</a>, we found that using a particular sedative at night can increase the risk for heart damage.</p>
<h2>Chronotherapeutic drug delivery</h2>
<p>The concept of chronotherapy isn’t new. For example, <a href="https://doi.org/10.1016/0014-5793(69)80210-3">over 50 years ago</a>, researchers found that the cholesterol drug <a href="https://www.ncbi.nlm.nih.gov/books/NBK532919/">simvastatin</a> is <a href="https://doi.org/10.3390/pharmaceutics8020013">more effective</a> at lowering triglyceride and cholesterol levels when taken at night rather than during the day. This is because the liver enzyme these drugs target is more active at night. As a result, the Food and Drug Administration recommends taking simvastatin in the evening. </p>
<p>Similarly, research in the 1990s showed that taking time of day into account when administering a combination chemotherapy could <a href="https://doi.org/10.1093/jnci/86.21.1608">increase its effectiveness and reduce treatment toxicity</a> for colorectal cancer patients. This is because cancer cells divide at different rates over the course of the day. The rate that the body metabolizes drugs also varies over a 24-hour cycle.</p>
<p>Other examples include the over-the-counter acid reflux medication <a href="https://doi.org/10.1111/j.1365-2036.1995.tb00440.x">omeprazole</a> and <a href="https://doi.org/10.1080/08037051.2022.2142512">blood pressure medications</a> that work best when taken before bedtime or in the evening, respectively.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/uOcpsXMJcJk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Many factors can affect how well a drug will work for each person.</span></figcaption>
</figure>
<p>Taking medications at the wrong time can even cause harm. My colleagues and I wondered whether midazolam, the most common sedative used in surgical procedures worldwide, might <a href="https://doi.org/10.1073/pnas.1201734109">interfere with the internal clock</a> that protects the heart at night. Currently, there are no guidelines regarding when midazolam should be administered.</p>
<p>When we analyzed data from 50 medical institutions for the occurrence of heart damage during surgical procedures from 2014 to 2019, we found that taking midazolam during overnight surgeries may increase the odds of <a href="https://doi.org/10.3389%2Ffcvm.2022.982209">heart damage in healthy patients</a> by over threefold.</p>
<h2>Timing matters</h2>
<p>More research is needed to determine the best times to administer treatments for different diseases. Taking time of day into account might require <a href="https://doi.org/10.1126/science.aax7621">reformulating some medications</a> that last for more than a 24-hour time period in the body.</p>
<p>As of 2019, the FDA has recommendations for <a href="https://doi.org/10.1126/science.aax7621">only four</a> of the 50 currently most prescribed medications to be given at a specific time of day. Considering that the top 10 highest-grossing drugs in the U.S. help only <a href="https://doi.org/10.1038/520609a">between 1 in 25 and 1 in 4</a> of the people who take them, I believe that taking drug timing into account could help make treatments more effective and help more people worldwide.</p><img src="https://counter.theconversation.com/content/194906/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tobias Eckle receives funding from the NIH.</span></em></p>There is a best time to take your medications, but your doctor may not know when that is. Researchers are still figuring it out, one drug at a time.Tobias Eckle, Professor of Anesthesiology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1834212022-06-29T12:04:48Z2022-06-29T12:04:48ZMany drugs can’t withstand stomach acid – a new delivery method could lead to more convenient medications<figure><img src="https://images.theconversation.com/files/470674/original/file-20220623-60671-hmb5da.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A new polymer could help the medicine go down easier.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/stomach-shaped-with-medication-royalty-free-image/1206781656">Hiroshi Watanabe/DigitalVision via Getty Images</a></span></figcaption></figure><p>For patients and physicians, taking medications orally is often the most desirable way to administer drugs. Among other <a href="https://www.merckmanuals.com/home/drugs/administration-and-kinetics-of-drugs/drug-administration#">advantages</a>, swallowing a pill is safer, more convenient and less invasive compared to injections or other ways to take a drug. </p>
<p>But one of the challenges oral pills face is getting digested by the stomach before they can deliver their payloads and carry out their intended effects. Because drugs that are degraded in the stomach are <a href="https://doi.org/10.3390%2Fpharmaceutics11030129">less effective</a>, many treatments are currently unable to be taken by mouth.</p>
<p>As researchers in <a href="https://scholar.google.com/citations?user=azZT0AkAAAAJ&hl=en">polymer science</a> and <a href="https://scholar.google.com/citations?user=d8rx9j8AAAAJ&hl=en">bioengineering</a>, we wanted to figure out a way to deliver drugs so that they could withstand stomach acid but still dissolve at the right place. In our <a href="https://doi.org/10.1038/s41467-022-29851-y">recently published paper</a>, we believe we have developed a new material that can help drugs do just that.</p>
<h2>Oral drug challenges</h2>
<p>Oral drugs are primarily <a href="https://www.merckmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-absorption#">absorbed in the small intestine</a>, where they subsequently enter the bloodstream and travel to the rest of the body. In order for a drug to get to the small intestine, however, it must first get past the <a href="https://www.healthline.com/health/how-strong-is-stomach-acid#strength">highly acidic environment</a> of the stomach, which can deteriorate medications before they can be absorbed. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/4rY3X4xafs0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This is what pills look like when they dissolve in water.</span></figcaption>
</figure>
<p>To compensate for degradation in the stomach, oral medications typically come in doses that are <a href="https://doi.org/10.1016/j.ejps.2021.105812">higher than necessary</a>. This strategy works for many common <a href="https://scholarblogs.emory.edu/techtransfer/2021/02/the-differences-between-small-molecule-drugs-and-biological-drugs/">small-molecule drugs</a> that have a low mass. They are often more stable and can more easily enter cells compared to other types of drugs. However, increasing dosage is not a viable approach for treatments that easily build up to toxic levels, are too sensitive to the acidity of the stomach or are very costly.</p>
<h2>A stomach acid-resistant material</h2>
<p>To help drugs withstand the harsh environment of the stomach, our research team developed a new type of material called <a href="https://doi.org/10.1038/s41467-022-29851-y">polyzwitterionic complexes, or pZCs</a>. pZCs are composed of two types of <a href="https://www.britannica.com/science/polymer">polymers</a>, or large molecules made of a string of repeating smaller molecules. As the name suggests, pZCs are made of <a href="https://doi.org/10.1021/acsapm.9b00897">polyzwitterions</a>, which are both positively and negatively charged, and <a href="https://doi.org/10.1021/acs.macromol.7b01929">polyelectrolytes</a>, which are exclusively positive or negative. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram comparing monomers, dimers, trimers and oligomers with polymers" src="https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/470676/original/file-20220623-51620-pjglx7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=471&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Polymers are made of individual units that repeat and combine in different ways.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/vector-scientific-illustration-of-monomer-royalty-free-illustration/1299060265">petrroudny/iStock via Getty Images</a></span>
</figcaption>
</figure>
<p>Through a process called <a href="https://doi.org/10.1002/9781119290971.ch7">complex coavcervation</a> that joins oppositely charged molecules, these two polymers self-assemble to form pZC droplets that are sensitive to acidity. In principle, these droplets could encapsulate and protect a therapeutic cargo as it travels through the highly acidic stomach, but disassemble and release the drug upon reaching the <a href="https://doi.org/10.1136%2Fgut.29.8.1035">more neutral environment</a> of the small intestine.</p>
<p>We first tested whether the pZC droplets were able to encapsulate a protein as a test cargo. Once we were successfully able to place the cargo in the droplet, we then measured how much protein cargo was released in varying levels of acidity through <a href="https://www.nist.gov/programs-projects/spectrophotometry">spectrophotometry</a>, a method that uses light absorption to measure the amount of substance present in a sample. We found that the pZC droplets retained their protein cargo in acidic conditions and steadily released it as acidity decreased.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram depicting pZC associating at low pH levels and dissociating at high pH levels as it travels through the gastrointestinal tract" src="https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=445&fit=crop&dpr=1 600w, https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=445&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=445&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=559&fit=crop&dpr=1 754w, https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=559&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/470828/original/file-20220624-24-xso94d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=559&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">pZC is designed to stay enveloped around its drug cargo in highly acidic environments, as in the stomach, and disassemble in less acidic environments, as in the small intestine.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1038/s41467-022-29851-y">Khatcher Margossian</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Making drugs more convenient</h2>
<p>We believe that our pZC system can enable researchers to develop new and improved ways to deliver drugs through the gastrointestinal tract. Our future work will focus on better understanding how pZCs behave as their chemical properties change in different conditions. We are also experimenting with different types of polymers and drug cargoes.</p>
<p>Our hope is that our methods and conceptual framework will one day increase the number and variety of drugs that can be taken orally, making it more convenient to take your medicine and improving the lives of patients.</p><img src="https://counter.theconversation.com/content/183421/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Khatcher O. Margossian has received funding from the National Science Foundation. No additional conflicts of interest are declared.</span></em></p><p class="fine-print"><em><span>Murugappan Muthukumar receives funding from the National Science Foundation and the Air Force Office of Scientific Research.</span></em></p>While pills are more practical than injections or infusions, digestion in the stomach prevents many drugs from being taken orally. Better drug design could change this.Khatcher O. Margossian, MD/PhD Candidate in Polymer Science and Engineering, UMass AmherstMurugappan Muthukumar, Professor in Polymer Science and Engineering, UMass AmherstLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1824882022-06-17T12:33:45Z2022-06-17T12:33:45ZHow do drugs know where to go in the body? A pharmaceutical scientist explains why some medications are swallowed while others are injected<figure><img src="https://images.theconversation.com/files/469333/original/file-20220616-24-uw9qbz.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While pills come in many shapes and sizes, they all eventually reach your bloodstream and travel throughout your body.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/pop-art-medicine-pill-or-tablet-icon-royalty-free-illustration/1264546155">Vadim Sazhniev/iStock via Getty Images</a></span></figcaption></figure><p>When you take aspirin for a headache, how does the aspirin know to travel to your head and alleviate the pain?</p>
<p>The short answer is, it doesn’t: Molecules can’t transport themselves through the body, and they don’t have control over where they eventually end up. But researchers can chemically modify drug molecules to make sure that they bind strongly to the places we want them and weakly to the places we don’t.</p>
<p>Pharmaceutical products contain more than just the active drug that directly affects the body. Medications also include “inactive ingredients,” or molecules that enhance the stability, absorption, flavor and other qualities that are critical to allowing the drug to do its job. For example, the aspirin you swallow also has ingredients that both prevent the tablet from fracturing during shipping and help it break apart in your body.</p>
<p>As a <a href="https://www.researchgate.net/profile/Thomas-Anchordoquy">pharmaceutical scientist</a>, I’ve been studying <a href="https://www.nibib.nih.gov/science-education/science-topics/drug-delivery-systems-getting-drugs-their-targets-controlled-manner">drug delivery</a> for the past 30 years. That is, developing methods and designing nondrug components that help get a medication where it needs to go in the body. To better understand the thought process behind how different drugs are designed, let’s follow a drug from when it first enters the body to where it eventually ends up.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Shelves of orange pill bottles" src="https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/469339/original/file-20220616-20-4bvdhf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Drugs aren’t sentient, but good design can help them get where doctors and patients want them to go.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/rows-of-pill-bottles-on-shelves-in-pharmacy-royalty-free-image/73092126">Andersen Ross/DigitalVision via Getty Images</a></span>
</figcaption>
</figure>
<h2>How drugs are absorbed in the body</h2>
<p>When you swallow a tablet, it will initially dissolve in your stomach and intestines before the drug molecules are <a href="https://www.britannica.com/science/drug-chemical-agent/Types-of-drugs">absorbed into your bloodstream</a>. Once in the blood, it can circulate throughout the body to access different organs and tissues.</p>
<p>Drug molecules affect the body by <a href="https://open.lib.umn.edu/pharmacology/chapter/introduction-to-drug-receptor-interactions-and-pharmacodynamics/">binding to different receptors</a> on cells that can trigger a particular response. Even though drugs are designed to target specific receptors to produce a desired effect, it is impossible to keep them from continuing to circulate in the blood and binding to nontarget sites that potentially cause unwanted side effects.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/uOcpsXMJcJk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Many factors, like your age, genetics and diet, can affect how well your body processes a drug.</span></figcaption>
</figure>
<p>Drug molecules circulating in the blood also degrade over time and eventually leave the body in your urine. A classic example is the strong smell your urine might have after you eat asparagus because of how quickly your kidney clears <a href="https://theconversation.com/that-distinctive-springtime-smell-asparagus-pee-94696">asparagusic acid</a>. Similarly, <a href="https://www.getthegloss.com/article/ask-the-doctor-why-do-vitamins-make-my-pee-yellow">multivitamins</a> typically contain riboflavin, or vitamin B2, which causes your urine to turn bright yellow when it is cleared. Because how efficiently drug molecules can cross the intestinal lining can vary depending on the drug’s chemical properties, some of the drugs you swallow never get absorbed and are removed in your feces.</p>
<p>Because not all of the drug is absorbed, this is why some medications, like those used to treat high blood pressure and allergies, are <a href="https://www.healthymepa.com/2018/07/23/important-take-medications-time/">taken repeatedly</a> to replace eliminated drug molecules and maintain a high enough level of drug in the blood to sustain its effects on the body. </p>
<h2>Getting drugs to the right place</h2>
<p>Compared with pills and tablets, a more efficient way of getting drug into the blood is to inject it directly into a vein. This way, all the drug gets circulated throughout the body and avoids degradation in the stomach. </p>
<p>Many drugs that are given intravenously are “<a href="https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/what-are-biologics-questions-and-answers">biologics” or “biotechnology drugs</a>,” which include substances derived from other organisms. The most common of these are a type of cancer drug called <a href="https://my.clevelandclinic.org/health/treatments/22774-monoclonal-antibody-therapy">monoclonal antibodies</a>, proteins that bind to and kill tumor cells. These drugs are injected directly into a vein because your stomach can’t tell the difference between digesting a therapeutic protein and digesting the proteins in a cheeseburger.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Nurse checking infusion bag hanging on IV pole" src="https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/469317/original/file-20220616-24-tpqvb8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Sometimes the most effective way to deliver a drug is through an infusion.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/professional-black-head-nurse-wearing-face-mask-royalty-free-image/1321691597">gorodenkoff/iStock via Getty Images</a></span>
</figcaption>
</figure>
<p>In other cases, drugs that need very high concentrations to be effective, such as <a href="https://health.ucsd.edu/news/features/pages/2017-05-01-intravenous-antibiotics-q-and-a-ritter.aspx">antibiotics for severe infections</a>, can be delivered only through infusion. While increasing drug concentration can help make sure enough molecules are binding to the correct sites to have a therapeutic effect, it also increases binding to nontarget sites and the risk of side effects.</p>
<p>One way to get a high drug concentration in the right location is to apply the drug right where it’s needed, like rubbing an ointment onto a skin rash or using <a href="https://www.webmd.com/allergies/allergy-eye-drops">eyedrops for allergies</a>. While some drug molecules will eventually get absorbed into the bloodstream, they will be <a href="https://doi.org/10.1007/978-1-4471-3625-5_24">diluted enough</a> that the amount of drug that reaches other sites is very low and unlikely to cause side effects. Similarly, an inhaler delivers the drug directly to the lungs and avoids affecting the rest of the body.</p>
<h2>Patient compliance</h2>
<p>Finally, a key aspect in all drug design is to simply get patients to take medications in the right amounts at the right time. </p>
<p>Because remembering to take a drug several times a day is difficult for many people, researchers try to design drug formulations so they need to be <a href="http://dx.doi.org/10.1201/9781315111896-12">taken only once a day or less</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person taking out pills from pill box" src="https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/469327/original/file-20220616-15-393l9w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Taking medications as instructed can help increase their effectiveness and reduce the risk of side effects.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/senior-woman-took-out-the-pills-from-pill-container-royalty-free-image/1289013876">violetphoto/Moment via Getty Images</a></span>
</figcaption>
</figure>
<p>Similarly, pills, inhalers or nasal sprays are more convenient than an infusion that requires traveling to a clinic for a trained clinician to inject it into your arm. The less troublesome and expensive it is to administer a drug, the more likely it is that patients will take their medication when they need it. However, sometimes infusions or injections are the only effective way that certain drugs can be administered. </p>
<p>Even with all the science that goes into understanding a disease well enough to develop an effective drug, it is often up to the patient to make it all work as designed.</p><img src="https://counter.theconversation.com/content/182488/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tom Anchordoquy receives funding from the National Institutes of Health. </span></em></p>From tablets and patches to ointments and infusions, the best way to deliver a drug is the one that gets the right amount to the right place.Tom Anchordoquy, Professor of Pharmaceutical Sciences, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1022892018-08-29T18:02:01Z2018-08-29T18:02:01ZBrain implant could stop epilepsy seizures<figure><img src="https://images.theconversation.com/files/234039/original/file-20180829-195328-f75rh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/344282432?src=0qMPwIzLEtNMAGGfywpNHw-1-88&size=medium_jpg">SpeedKingz/Shutterstock</a></span></figcaption></figure><p>For many people who suffer from neurological disorders, such as epilepsy, there are no viable treatment options. In our <a href="http://advances.sciencemag.org/content/4/8/eaau1291">latest research</a>, we developed an implantable device that may one day offer relief. We show that the implant can treat problems in the brain, such as epileptic seizures, by delivering brain chemicals – known as neurotransmitters – directly to the cells in the brain that cause the problem.</p>
<p>The implant works by using an electric field to push neurotransmitters out of the device from an internal reservoir. This process, known as <a href="https://www.thoughtco.com/electrophoresis-definition-4136322">electrophoresis</a>, allows for precise control over the dose and timing of drug delivery, which is important for addressing intermittent disorders such as epilepsy. </p>
<p>This way of delivering drugs also has the advantage of not increasing the local pressure where the drug exits the device because the drug molecules are not in a solvent – they exit the device “dry”. This is important because it means the drug molecules (neurotransmitters in this case) can interact directly with the tissue surrounding the implant without causing damage to those cells or the surrounding tissue.</p>
<p>Researchers have <a href="http://advances.sciencemag.org/content/1/4/e1500039">previously shown</a> that this method for delivering drugs can be used to manage pain, with an implant that was placed in the spinal cord of rats. The novelty of our work, published in Science Advances, was to engineer an implant small enough to be implanted in the brain of mice. We also incorporated tiny sensors into the implant to allow us to monitor the local brain activity where the device was implanted. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=471&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Neurotransmitters are the brain’s chemical messengers.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/432573415?src=dOOXsUyelZUo17hUgHiTKQ-1-1&size=medium_jpg">Andrii Vodolazhskyi/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Using the on-board sensors, we could see the onset of seizure-like activity in mice. After a seizure was detected, we told the implant to send out inhibitory neurotransmitters to the brain tissue at the centre of the seizures. The neurotransmitters tell the cells in that tissue to stop propagating the seizure message to other cells. This stopped the seizures.</p>
<p>After finding that we could stop seizures, we wanted to see if we could prevent seizures altogether, rather than stop them after they have started. To test this, we started delivering the neurotransmitters before a dose of seizure-inducing chemicals was injected into the brain with a separate implant. These experiments showed that our implant could prevent any seizure-like activity from happening.</p>
<h2>Platform technology</h2>
<p>We are very excited because this is the first time anyone has seen that an electrophoretic drug delivery device can stop or prevent seizure-like activity. Also, we see this as a platform technology that could be adapted to help treat many different neurological disorders including epilepsy, Parkinson’s disease and brain tumours.</p>
<p>It is important to note that, so far, this device has only been tested in mice and rats. Judging from the time it has taken for other technologies to go from this stage to widespread clinical use, it is likely to be at least a decade before this technology would be widely available for humans. During this time much work will be done to prove the long-term viability of these implants for treating epilepsy as well as other neurological disorders.</p><img src="https://counter.theconversation.com/content/102289/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Proctor receives funding from the University of Cambridge where he is a research associate and Borysiewicz Biomedical Sciences fellow in the Department of Engineering.
</span></em></p>New approach to preventing seizures proves effective in mice.Christopher Proctor, Research Associate in the Fabrication and Validation of Implantable Ion Pumps, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/661492016-10-21T09:08:40Z2016-10-21T09:08:40ZWater-retaining hydrogels – the unsung heroes of medicine<figure><img src="https://images.theconversation.com/files/142022/original/image-20161017-12431-13qfnoq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Hydrogel beads.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-377290516/stock-photo-color-balls-hydrogel-beads.html?src=KSZUGGc9lGh983qfGtd6rA-1-0">Baranov E/Shutterstock.com</a></span></figcaption></figure><p>Hydrogels, materials that can absorb and retain large quantities of water, could revolutionise medicine. Our bodies contain up to 60% water, but <a href="http://www.nature.com/nmat/journal/v15/n2/full/nmat4463.html">hydrogels can hold up to 90%</a>. It is this similarity to human tissue that has led researchers to examine if these materials could be used to improve the treatment of a range of medical conditions including heart disease and cancer.</p>
<p>These days hydrogels can be found in many everyday products, from disposable nappies and soft contact lenses to plant-water crystals. But the history of hydrogels for medical applications started in the 1960s. Scientists developed artificial materials with the ambitious goal of using them in permanent contact applications – ones that are implanted in the body permanently. </p>
<h2>Drug delivery</h2>
<p>One of the most exciting clinical applications being tested is in drug delivery. People with type 1 diabetes need to constantly inject themselves with insulin in order to control their blood sugar levels. But hydrogels could dispense with that need. </p>
<p>Researchers are working on hydrogels that contain insulin which can be injected under the skin. This creates a <a href="http://www.sciencedirect.com/science/article/pii/S0142961208001002">deposit of insulin within the body</a>. Because these materials contains a large amount of water, the insulin can move from the interior of the hydrogel to the exterior producing a slow release of the hormone. When all the insulin is released, the hydrogel is naturally disposed of by the body. In this way, multiple insulin injections can be replaced with a single hydrogel injection. </p>
<p>Others have sought to get rid of the need for insulin injections by trying to develop a tablet containing insulin which can be <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059524">taken orally</a>. One of the main challenges is that insulin tends to be destroyed in the stomach before it can reach the intestines to be absorbed into the body. Scientists are using hydrogels to try to <a href="http://www.sciencedirect.com/science/article/pii/S0168365912007596">solve this problem</a>. By creating hydrogels which can protect the insulin from the stomach acids and adhere temporarily to the walls of the intestine, the insulin can be safely absorbed into the body, removing the need for an injection.</p>
<p>The treatment of cancer can also be improved through the use of hydrogels. Chemotherapy generally involves patients attending a hospital for treatment with the medicine administered either via injection or a drip. Researchers are attempting to reduce the cost of chemotherapy and improve patients’ quality of life by exploring the use of hydrogels as a <a href="http://www.sciencedirect.com/science/article/pii/S0168365908000242">means of delivering this treatment</a> too. Similar to diabetes, researchers are investigating whether these medicines can be delivered orally. This would reduce the need for patients to attend hospital for treatment and lessen the cost of providing chemotherapy. However, as anti-cancer drugs cannot be easily dissolved in water, researchers need to find a way to improve the ability of the body to absorb these drugs when they are <a href="http://www.sciencedirect.com/science/article/pii/S0142961214004979">taken orally</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/142542/original/image-20161020-8865-kdxrlc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/142542/original/image-20161020-8865-kdxrlc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142542/original/image-20161020-8865-kdxrlc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142542/original/image-20161020-8865-kdxrlc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142542/original/image-20161020-8865-kdxrlc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142542/original/image-20161020-8865-kdxrlc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142542/original/image-20161020-8865-kdxrlc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Hydrogels could improve cancer patients’ quality of life.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-222626152/stock-photo-cancer-woman-lying-in-bed-supported-by-mum.html?src=4wry83NwDMIt-UiYjvcopw-1-37">ESB Professional/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Tissue repair</h2>
<p>The uses of hydrogels are not limited to drug delivery. Recently, a group of researchers from the University of Pennsylvania demonstrated how hydrogels can be used to help <a href="https://www.acs.org/content/acs/en/pressroom/newsreleases/2016/august/after-the-heart-attack-injectable-gels-could-prevent-future-heart-failure-video.html">prevent damage to the heart</a>. People are at a greater risk of experiencing heart damage after a heart attack as the organ becomes enlarged and its walls tend to narrow and become scarred. Injecting hydrogels into the heart’s walls after an attack provide mechanical support and stabilises the damaged area.</p>
<p>Hydrogels can also be used to improve tissue healing and tissue regeneration by delivering stem cells or proteins – inside a wound or broken bone – to <a href="https://www.ncbi.nlm.nih.gov/pubmed/20882499">stimulate tissue regrowth</a>.</p>
<p>At Queen’s University Belfast, we are also working on several different medical applications of hydrogels including <a href="https://theconversation.com/explainer-what-are-microneedles-and-why-do-we-need-them-54623">hydrogel microneedle patches</a>, for the delivery of medicines through the skin, and a hydrogel capable of <a href="http://www.irishtimes.com/news/science/queen-s-university-scientists-take-fight-to-hospital-superbugs-1.1901272">destroying hospital superbugs</a> by preventing bacteria to form colonies. There seems to be no end to the versatility of this wonderful substance.</p><img src="https://counter.theconversation.com/content/66149/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eneko Larraneta does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Humble hydrogels could one day replace hypodermic needles and repair damaged hearts.Eneko Larraneta, Lecturer in Pharmaceutical Sciences, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/605802016-06-07T12:21:14Z2016-06-07T12:21:14ZFrom living computers to nano-robots: how we’re taking DNA beyond genetics<figure><img src="https://images.theconversation.com/files/125408/original/image-20160606-13045-ea307k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Molecular computer</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>DNA is one of the most amazing molecules in nature, providing a way to carry the instructions needed to create almost any lifeform on Earth in a microscopic package. Now scientists are finding ways to push DNA even further, using it not just to store information but to create physical components in a range of biological machines.</p>
<p><a href="https://ghr.nlm.nih.gov/primer/basics/dna">Deoxyribonucleic acid or “DNA”</a> carries the genetic information that we, and all living organisms, use to function. It typically comes in the form of the famous double-helix shape, made up of two single-stranded DNA molecules folded into a spiral. Each of these is made up of a series of four different types of molecular component: adenine (A), guanine (G), thymine (T), and cytosine (C).</p>
<p>Genes are made up from different sequences of these building block components, and the order in which they appear in a strand of DNA is what encodes genetic information. But by precisely designing different A,G,T and C sequences, scientists have recently been able to develop new ways of <a href="http://www.nature.com/nature/journal/v440/n7082/abs/nature04586.html">folding DNA</a> into different origami shapes, beyond the conventional double helix.</p>
<p>This approach has opened up new possibilities of using DNA beyond its genetic and biological purpose, turning it into a Lego-like material for building objects that are just a few billionths of a metre in diameter (nanoscale). DNA-based materials are now being used for a variety of applications, ranging from templates for electronic nano-devices, to ways of precisely carrying drugs to diseased cells.</p>
<h2>DNA-based nanothermometers</h2>
<p>Designing electronic devices that are just nanometres in size opens up all sorts of <a href="https://theconversation.com/five-ways-nanotechnology-is-securing-your-future-55254">possible applications</a> but makes it harder to spot defects. As a way of dealing with this, researchers at the University of Montreal have used DNA to create ultrasensitive <a href="http://pubs.acs.org/doi/abs/10.1021/acs.nanolett.6b00156">nanoscale thermometers</a> that could help find minuscule hotspots in nanodevices (which would indicate a defect). They could also be used to monitor the temperature inside living cells.</p>
<p>The nanothermometers are made using loops of DNA that act as switches, folding or unfolding in response to temperature changes. This movement can be detected by attaching optical probes to the DNA. The researchers now want to build these nanothermometers into larger DNA devices that can work inside the human body.</p>
<h2>Biological nanorobots</h2>
<p>Researchers at Harvard Medical School have used DNA to <a href="http://science.sciencemag.org/content/335/6070/831">design and build</a> a nanosized robot that acts as a drug delivery vehicle to target specific cells. The nanorobot comes in the form of an open barrel made of DNA, whose two halves are connected by a hinge held shut by special DNA handles. These handles can recognise combinations of specific proteins present on the surface of cells, including ones associated with diseases. </p>
<p>When the robot comes into contact with the right cells, it opens the container and delivers its cargo. When applied to a mixture of healthy and cancerous human blood cells, these robots showed the ability to target and kill half of the cancer cells, while the healthy cells were left unharmed.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/125402/original/image-20160606-13074-12bg2xg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/125402/original/image-20160606-13074-12bg2xg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125402/original/image-20160606-13074-12bg2xg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125402/original/image-20160606-13074-12bg2xg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125402/original/image-20160606-13074-12bg2xg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125402/original/image-20160606-13074-12bg2xg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125402/original/image-20160606-13074-12bg2xg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">DNA barrel.</span>
<span class="attribution"><a class="source" href="http://www.eurekalert.org/multimedia/pub/40848.php">Campbell Strong, Shawn Douglas, & Gaël McGill</a></span>
</figcaption>
</figure>
<h2>Bio-computers in living animals</h2>
<p>Because DNA structures can act as switches, moving from one position to another and back again, they can be used to perform the logical operations that make computer calculations possible. Researchers at Harvard and Bar-Ilan University in Israel have used this principle to build different nanoscale robots that can interact with each other, using their DNA switches to react to and produce different signals.</p>
<p>What’s more, the scientists <a href="http://www.nature.com/nnano/journal/v9/n5/full/nnano.2014.58.html">implanted the robots</a> into a living animal, in this instance a cockroach. This allowed them to develop a novel type of biological computer that can control the delivery of therapeutic molecules inside the cockroach by switching elements of their structure “on” or “off”. A trial of these DNA nanorobots is now scheduled to <a href="http://singularityhub.com/2015/01/08/can-dna-nanobots-successfully-treat-cancer-patient-first-human-trial-soon/">take place in humans</a>.</p>
<h2>Light-harvesting antennas</h2>
<p>As well as creating minuscule machines, DNA can provide a way for us to copy natural processes at the nanoscale. For example, nature can capture energy from the sun using photosynthesis to convert light into chemical energy, which acts as fuel for plants and other organisms (and the animals that eat them). Researchers at Arizona State University and the University of British Columbia have now built a three-arm DNA structure that can <a href="http://pubs.acs.org/doi/abs/10.1021/ja509018g">capture and transfer light</a> that mimics this process.</p>
<p>Photosynthesis occurs in living organisms thanks to tiny antennas made up of a large number of pigment molecules at specific orientations and distances from each other, which are able to absorb visible light. The artificial DNA-based structures act as similar antennas, controlling the position of specific dye molecules that absorb the light energy and channel it to a reaction centre where it is converted into chemical energy. This work could pave the way for devices capable of more efficiently using the most abundant source of energy we have at our disposal: sunlight.</p>
<p>So what’s next for DNA nanotechnology? It is hard to know but, with DNA, nature has given us a very versatile tool. It is now up to us to make the best use of it.</p><img src="https://counter.theconversation.com/content/60580/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matteo Palma receives funding from the Engineering and Physical Research Council and the Royal Society of Chemistry.</span></em></p>Scientists are using DNA to build exciting new nanotechnologies that could change everything from electronics to energy.Matteo Palma, Queen Mary University of LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/546232016-03-18T13:43:08Z2016-03-18T13:43:08ZExplainer: what are microneedles and why do we need them?<figure><img src="https://images.theconversation.com/files/115097/original/image-20160315-9279-1nzdv5v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Microscope image of polymeric microneedles.</span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><p>Microneedles are tiny needles, small enough that they are measured in millionths of a metre (μm), designed to deliver medicines. But “needles” is perhaps a misnomer. In terms of how they work, microneedles have more in common with transdermal patches, such as those used <a href="http://www.nhs.uk/smokefree/help-and-advice/prescription-medicines">to deliver nicotine</a> to help people give up smoking, than they do with traditional hypodermic needles.</p>
<p>The skin does an excellent job of keeping things out. And the part of the skin that provides the most protection from would-be penetrants is the outer 10-50μm layer of skin called the “stratum corneum”. When it comes to drug delivery, the aim is to get the medicine through this layer. It was from this problem that the concept of microneedles was born.</p>
<p>By the late 1990s, research groups worldwide were making microneedles from materials such as metal, silicon and glass. By bypassing the outer layer of the skin, microneedles were able to create an easier passage to the rich blood supply in the lower dermal layers, allowing easy, pain-free delivery of a wide range of medicines across the skin. </p>
<h2>How do microneedles work?</h2>
<p>Typically grouped together in a large number, microneedles are designed to be applied to the skin like a patch. When pressed onto the skin surface, the needles are able to cross the very outermost layer of the skin, which then creates microscopic pores, allowing the medicine to enter the body. Because the needles are very small, the dermal nerves and blood vessels aren’t affected, so there is no pain or bleeding when the patch is applied. Instead, patches covered with microneedles have been described as feeling similar to Velcro or a cat’s tongue when touched.</p>
<p>The unique <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627464/">microneedle arrays</a> that our research group at Queen’s University Belfast is working on are made from a polymeric material. It’s the same material that, in another form, is used help dental patients’ dentures stick to their gums. What we have done is change this adhesive material into microneedles which are able to take up fluid and swell but not actually dissolve. </p>
<p>The needles are hard when they’re dry, so they can be easily applied to the skin. The medicine is held in a reservoir adjacent to the microneedles. When inserted, the microneedles draw in the fluid that bathes cells, and they then begin to swell. This opens up the structure of the material. When the fluid from the skin enters the patch, it dissolves the reservoir that holds the medicine, which is then able to move through the microneedles into the dermal layers of the skin that is rich in blood vessels. These blood vessels then transport the medicine to the rest of the body.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/115471/original/image-20160317-30244-18e7vv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/115471/original/image-20160317-30244-18e7vv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=390&fit=crop&dpr=1 600w, https://images.theconversation.com/files/115471/original/image-20160317-30244-18e7vv1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=390&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/115471/original/image-20160317-30244-18e7vv1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=390&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/115471/original/image-20160317-30244-18e7vv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=490&fit=crop&dpr=1 754w, https://images.theconversation.com/files/115471/original/image-20160317-30244-18e7vv1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=490&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/115471/original/image-20160317-30244-18e7vv1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=490&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Diagram showing microneedle application to the skin and the swelling of the array.</span>
</figcaption>
</figure>
<h2>What can microneedles be used for?</h2>
<p>One of the most promising uses for microneedles is the delivery of vaccines. As one of the greatest healthcare interventions, vaccines are a global health priority, but they are not without their challenges. For a vaccine to remain stable it needs to be kept refrigerated from the time of manufacture to when it is given (this is known as the “cold chain”). Any breaks in the cold chain (that is, temperatures above or below 2°C to 8°C) can cause the vaccine to become inert.</p>
<p>The World Health Organisation estimates that a half of all vaccines produced globally <a href="http://www.pphsn.net/outbreak/vaccine_management/who-monitoring_vaccine_wastage_at_the_country_level.pdf">are wasted</a> and a large proportion of this wastage is due to failure of the cold chain, especially in developing countries. </p>
<p>Microneedles have a distinct advantage over liquid vaccines. With microneedles, vaccines can be prepared in a dry state, doing away with the need for refrigeration. These dry vaccines are stable at ambient temperatures which would greatly reduce waste. It would be easier to transport and store dry microneedle vaccines, and they’d probably also be cheaper to produce. </p>
<p>Microneedles offer an opportunity for the future of vaccination, particularly needed in the developing world. By investigating this new delivery approach, the provision of lifesaving vaccines may be able to be extended to those who need them the most.</p><img src="https://counter.theconversation.com/content/54623/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Helen Quinn received PhD funding from the Department of Education and Learning in Northern Ireland to complete her doctoral research.
Ryan Donnelly has received funding from the BBSRC, EPSRC, MRC, The Wellcome Trust, The Royal Society and the pharmaceutical and medical devices industries.</span></em></p>Half of all vaccines are wasted. Microneedles may be one way to tackle the problem.Helen Quinn, Postdoctoral research fellow, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/422012015-05-22T14:11:48Z2015-05-22T14:11:48ZUltrasound-activated bubbles could help make cancer drugs more effective and less nasty<figure><img src="https://images.theconversation.com/files/82558/original/image-20150521-985-1gxrao3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nanoparticles: small but deadly... to cancer</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Despite extraordinary advances in new drugs and biotechnology, cancer is still one of the leading causes of death worldwide.</p>
<p>In many cases, the problem lies not with the drugs but rather the difficulty in successfully delivering them to the site of a tumour. In healthy tissue there is a regular structure of blood vessels supplying oxygen and nutrients to cells, which divide and grow at a steady rate. In cancerous tumours, however, cells divide and grow in an unregulated way, producing a <a href="http://www.ncbi.nlm.nih.gov/pubmed/2292138">chaotic vessel structure</a> and regions of tissue with little or no blood supply.</p>
<p>This means when drugs are ingested or injected into the blood stream, they don’t reach all parts of the tumour and there is a high risk of cancer recurring after treatment. On top of this, the <a href="http://www.ncbi.nlm.nih.gov/pubmed/9018236">pressure inside</a> many tumours prevents a drug from being absorbed from the blood, meaning only a very small fraction of it is actually delivered. The rest of the drug circulates around the body and is eventually absorbed by healthy tissue, often leading to intolerable side effects.</p>
<p>One of the major goals of the research being carried out in the <a href="http://www.ibme.ox.ac.uk">Oxford Institute of Biomedical Engineering</a> (IBME) is to develop new methods for delivering anti-cancer drugs that overcome these barriers. While engineers are perhaps more commonly thought of in the context of large construction projects, we are using precisely the same combination of applied science and problem solving.</p>
<h2>Building nanoparticles</h2>
<p>There is a formidable series of challenges to address to solve this problem. First, we need to encapsulate the drug to prevent it from interacting with healthy tissue and/or deactivating before reaching the tumour. Second, we need a way to deliver the drug to the tumour to maximise the concentration it receives.</p>
<p>Third, we need a mechanism for releasing the drug on demand once it has built up within the tumour. Fourth, we need to ensure the released drug is evenly spread throughout the tumour. And finally, we need to be able to monitor the treatment from outside the body.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Taking the fight to cancer.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Our team at the IBME has developed a range of new techniques for creating tiny particles into which we can insert drugs with a high degree of precision. And we have tried a <a href="http://www.ncbi.nlm.nih.gov/pubmed/18261822">variety of methods</a> to make the particles release the drug. These include using materials that are sensitive to the pH change within a tumour and materials that break down upon heating or undergo a phase change (from a solid to a liquid or liquid to a gas).</p>
<p>But one of the most versatile means of triggering drug release is by firing a beam of <a href="http://www.ncbi.nlm.nih.gov/pubmed/23121385">ultrasonic vibrations</a> at the particles. Widely used as an <a href="http://www.nhs.uk/conditions/ultrasound-scan/pages/introduction.aspx">imaging method</a>, ultrasound can be used from outside the body and, unlike light or heat, can be tightly focused to produce highly localised effects.</p>
<p>In order to produce particles that respond to ultrasound, we have to include in them a gas or a liquid that easily vaporises. When exposed to the ultrasound, the gas/liquid will undergo a rapid expansion and force the drug out of the particle.</p>
<h2>Ultrasound activated bubbles</h2>
<p>This process generates a pulsating gas or vapour bubble that has several other significant benefits for drug delivery. The motion of the bubble produced by the ultrasound field helps to drive the drug out of the blood vessels and deep into the surrounding tumour. We have shown that bubbles can push drugs <a href="http://www.ibme.ox.ac.uk/research/non-invasive-therapy-drug-delivery/enhanced-drug-delivery">up to four times deeper</a> into tissue than they would normally diffuse, sufficient to achieve a uniform spread throughout a tumour.</p>
<p>There is also a growing body of research that shows microbubbles and ultrasound make cancer cells more permeable to drugs, speeding up the rate at which they work and ultimately cell death. The microbubbles’ motion produces a secondary ultrasound signal that can be detected outside the body. This means the location and activity of the particles can be <a href="http://www.ncbi.nlm.nih.gov/pubmed/25564961">continuously monitored</a>, providing real-time feedback on the progress of the treatment.</p>
<p>Our aim over the next five years is to translate these developments into clinical use. The work will focus on improving the delivery of four classes of drug that have shown enormous potential but that currently struggle to get inside a tumour and/or have unacceptable side effects. By combining our expertise in encapsulation with the use of ultrasound and shockwaves, we hope to create more effective drugs that can be delivered straight to the location of a tumour and monitored with advanced imaging techniques.</p>
<p><em>This article is adapted from the 2015 IET A. F. Harvey Prize Lecture</em></p><img src="https://counter.theconversation.com/content/42201/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eleanor Stride is a non-executive director of AtoCap Ltd. She receives funding from the Engineering and Physical Sciences Research Council, Cancer Research UK, Multiple Scelerosis Society.</span></em></p>New research could into nanoparticles could help deliver drugs straight to the site of tumours and make them more effective when they get there.Eleanor Stride, Professor of Engineering Science, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/358722015-01-06T11:19:19Z2015-01-06T11:19:19ZHow scorpion venom could yield new cancer treatment<figure><img src="https://images.theconversation.com/files/68210/original/image-20150105-13843-16kodql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ok, that's not the way to extract it.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/fabriceh_com/1053268909">fabriceh_com</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p>In the development of new drugs, taking something from nature and modifying it has been a successful tactic employed by medicinal chemists for years. Now, with the help of nanotechnology, researchers are turning once-discarded drug candidates into usable drugs.</p>
<p>An estimated <a href="http://www.scripps.edu/shen/NPLI/whynaturalproducts.html">40% of clinically approved drugs</a> fall into the category where either the natural compound itself or a modified version is the approved drug. These include statins (found in bacterial secretions) used to lower cholesterol, quinines (found in cinchona trees) as anti-malarials and paclitaxel (found in yew trees) as anti-cancer medication.</p>
<p>Many of these natural products are toxins produced by plants or animals as a form of defence. And scorpion venom has been gaining interest as a source of new drugs. It contains a mixture of biological chemicals called peptides, some of which are known to trigger cell death by forming pores in biological membranes. Cell death can be useful if we are able to target, say, tumour cells to auto-destruct.</p>
<p>These toxins can have very potent effects. For instance, one particular small peptide, known as TsAP-1, isolated from the Brazilian yellow scorpion (<em>Tityus serrulatus</em>), has both <a href="http://www.sciencedirect.com/science/article/pii/S0300908413001648">anti-microbial and anti-cancer properties</a>.</p>
<p>However, harnessing this kind of power for clinical good has so far been challenging because these toxins kill both tumours and healthy cells. One method to control such toxicity is through using <a href="https://theconversation.com/lack-of-new-drugs-is-being-overcome-by-new-ways-of-delivering-old-ones-33109">nanotechnology to build specially made drug-delivery vehicles</a>. If successful, the toxic drug is released to kill only unwanted tissues in a body.</p>
<p>One such attempt has been made by Dipanjan Pan at the University of Illinois at Urbana-Champagne. In a study published in the journal <a href="http://pubs.rsc.org/en/content/articlelanding/2014/cc/c4cc04748f#!divAbstract">Chemical Communications</a>, scientists claim to have created spherical capsules to trap scorpion venom toxin TsAP-1. This encapsulated toxin, named NanoVenin, increases the drugs effectiveness at killing breast cancer cells by ten times. </p>
<p>This is an interesting development for two reasons. Firstly, the venom toxin in its natural form could not be used due to the lack of specificity and, secondly, the incorporation of the venom toxin in the nanoparticle caused a large increase in the drug’s potency, making it more clinically useful.</p>
<p>This form of the drug works on breast cancer cells, but it is not disease-specific yet. Researchers can modify its outer shell by, for example, attaching proteins that can make it selective towards certain types of cancers. It may also be possible to coat the nanoparticle in a biodegradable layer so as to trap its toxicity until it reaches the diseased area, where the layer degrades to reveal the toxin. </p>
<p>Such precise delivery can work on a “lock-and-key system” of highly precise biological structures. For instance, different types of cancer cells have characteristic secretions or outer proteins – the biodegradable layer of the drug can be built to recognise these specific secretions or proteins and then trigger the degradation process, allowing precise delivery of the drug.</p>
<p>Often effective drugs have been discovered but not commercialised due to delivery issues. Yet the latest developments in nanotechnology illustrate how once discarded drugs sourced from natural compounds can be brought off the shelf to fight disease.</p><img src="https://counter.theconversation.com/content/35872/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Benjamin Burke does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>In the development of new drugs, taking something from nature and modifying it has been a successful tactic employed by medicinal chemists for years. Now, with the help of nanotechnology, researchers are…Benjamin Burke, Molecular Imaging Post-Doctoral Research Assistant, University of HullLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/332712014-11-03T06:00:46Z2014-11-03T06:00:46ZHow the infamous Yellow Rain investigation has inspired a drug delivery innovation<figure><img src="https://images.theconversation.com/files/63203/original/tqn2fvrx-1414599137.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Agent Orange this ain't.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/omeuceu/3160296849/">omeuceu</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>The history of science is full of episodes when a seemingly ludicrous theory is ridiculed, but then slowly gathers evidence and support to move from the fringes to the heart of the scientific consensus. Examples include Darwin’s theory of evolution by natural selection, the theory of plate tectonics that control the movement of Earth’s crust and, most recently, the Big Bang theory of the birth of our universe. </p>
<p>All these theories, even though initially mocked, came from respectable academics. It is rare for someone from outside the relevant scientific circles to make a wild stab in the dark and hit upon something that just happens to have a thread of truth to it. But one of these occasions involved a US intelligence officer.</p>
<h2>Strange weather</h2>
<p>In September 1981 Alexander Haig, the then US secretary of state, made a stunning allegation. He <a href="http://cns.miis.edu/npr/pdfs/81tucker.pdf">claimed to have evidence</a> that Soviet-backed forces in Vietnam and Laos had been waging chemical warfare on villagers in those countries. A dossier, released shortly after, documented eye-witness accounts – dating back to 1977 – of aircraft spraying areas with a substance that left vegetation littered with small yellow spots. Far worse were reports of horrific symptoms in the exposed populations: people who suffered stomach cramps and vomiting, before dying. This, according to a lab the US government employed, was due to deadly trichothecene toxins present in the yellow material that rained down on the villagers.</p>
<p>The seriousness of the allegations – with the US accusing the Soviets of breaching the Geneva Protocol on the use of chemical weapons – warranted the corroboration of evidence. So samples of the yellow substance were re-tested in labs throughout the world. First military scientists at UK’s Porton Down – and then others – found something surprising: the “yellow rain” contained, primarily, pollen. </p>
<p>Stranger still, the pollen was not complete. It had been stripped of its proteins and contents, leaving a largely empty shell.</p>
<p>Faced with this unexpected finding, Sharon Watson, a US intelligence agent, <a href="http://belfercenter.ksg.harvard.edu/files/Meselsonchapter.pdf">proposed an explanation</a> for the role of pollen in the mix: that it had been added to aid the dispersal and delivery of the toxins.</p>
<p>As Watson told a Washington press briefing in 1982: the agent initially came down wet, where it was first exposed to the skin. As the toxins were dissolved in a solvent, they were absorbed by the skin very quickly. But as the agent dried, Watson said, “a second aerosol effect” was created from kicking up the particle-sized pollen-like dust, which then lodged in the bronchii of the lung. </p>
<p>Watson told the briefing:</p>
<blockquote>
<p>We’ve shown in studies with animals that the internasal LD-50 [the dose lethal to 50% of an exposed population] for the trichothecenes is much lower than we would have expected, and that the trichothecenes, if they come in contact with the mucous membrane, were very rapidly absorbed and are very toxic by this route. </p>
<p>So if you could bring the compound into contact with the mucous membranes of the bronchii, then it’s a very effective way of getting it across. So there are two different ways that the compound is absorbed. It’s [a] very clever, clever mixture.</p>
</blockquote>
<p>In short, the intelligence service thought using pollen made the poison a lot more effective. </p>
<h2>Local produce</h2>
<p>But where did it come from? The cause of the yellow rain turned out to be something much more mundane – <a href="http://www.nature.com/nature/journal/v306/n5938/pdf/306008a0.pdf">honey bee faeces</a>.</p>
<p>Closer inspection showed that the pollen matched that from the flora in the area it was collected and was indistinguishable from local bee poo. The hollowing out of the pollen and lack of proteins was due to the bees having digested the pollen, before it was defecated and left on the leaves. The heavy yellow rain was explained by bees emerging from hives en masse, as they are inclined to do after inclement weather, and defecating (they never do this in their hives). </p>
<p>Meanwhile, the same labs that identified the pollen also <a href="http://www.nature.com/nature/journal/v321/n6069/pdf/321459b0.pdf">failed to find any trace of trichothecence</a> mixed with the pollen, which left the US theory that the yellow rain was a diabolical means of delivering chemical weapons in tatters. Whatever trichothecene was detected may have been naturally occurring, because the fungi that produce it were common in South-East Asia. Some eye witnesses still <a href="http://www.radiolab.org/story/239549-yellow-rain/">insist that chemical attacks did occur</a>, but evidence doesn’t seem to support the use of pollen-based warfare as means of delivering those chemicals. Despite this, however, the US government hasn’t retracted its allegations, stating that the issue <a href="http://www.wikiwand.com/en/Yellow_rain#/Disputed_conclusions">hasn’t been fully resolved</a>.</p>
<h2>The grain of truth</h2>
<p>I always found this story with its scientific and political twists quite appealing. Little did I know that I would find myself working on Watson’s crazy idea about delivering chemicals using pollens. It turns out there was a grain of truth in it.</p>
<p>My colleagues and I have been stripping pollen spores down to leave the indigestible shell – to bees and man alike – called an exine. These exines are incredibly tough. They have even been found intact, along with fossils, in sedimentary rock. </p>
<p>We have loaded these empty pollen shells with a variety of compounds including <a href="http://pubs.rsc.org/en/content/articlehtml/2013/tb/c2tb00228k">drugs</a>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/20495964">edible oils</a> and <a href="http://www.ncbi.nlm.nih.gov/pubmed/19841803">medical imaging agents</a> to see if they can provide a new way of delivering these chemicals to places of interest in the human body. </p>
<p>Our results show that pollen capsules can indeed be used to <a href="https://theconversation.com/lack-of-new-drugs-is-being-overcome-by-new-ways-of-delivering-old-ones-33109">trap chemicals and deliver</a> them into the body. Exines provide chemical and physical protection to their surrogate cargoes. What’s more interesting is that exine shells appear to assist in the absorption of their contents across a mucous membrane. Just as Watson had suggested they might. The result, then, is a potential drug-delivery device, which was conceived by one US intelligence agent.</p><img src="https://counter.theconversation.com/content/33271/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Lorch does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The history of science is full of episodes when a seemingly ludicrous theory is ridiculed, but then slowly gathers evidence and support to move from the fringes to the heart of the scientific consensus…Mark Lorch, Senior Lecturer in Biological Chemistry, University of HullLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/331092014-10-27T19:09:44Z2014-10-27T19:09:44ZLack of new drugs is being overcome by new ways of delivering old ones<figure><img src="https://images.theconversation.com/files/62876/original/4r3xz33m-1414414464.jpg?ixlib=rb-1.1.0&rect=0%2C920%2C5000%2C3360&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The last resort.</span> <span class="attribution"><span class="source">Rashevskyi Viacheslav</span></span></figcaption></figure><p>Development of new drugs for treatment of disease is an expensive, time-consuming and labour-intensive effort for both pharmaceutical companies and academics. For the past 15 years, “cost per approval” of new drugs has increased steadily. As drug development infrastructure increases rapidly in the pharmaceutical industry and high-throughput screening and huge libraries of potential drugs become more common, is there another way to bring more therapeutics to clinic?</p>
<p>Many drugs have the drug-like effect we would want, but aren’t successful in humans. For example, some are too toxic, others are excreted too soon, broken down in the body too early or cannot pass nature’s boundaries. These limitations could be overcome through new ways of delivering drugs into the body.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=446&fit=crop&dpr=1 600w, https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=446&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=446&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=561&fit=crop&dpr=1 754w, https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=561&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/39685/original/6fbcctyt-1390405969.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=561&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p>With <a href="https://theconversation.com/why-there-may-be-fewer-truly-new-drugs-hitting-the-market-22315">fewer new drugs</a> being produced by the pharmaceutical industry, the field of drug delivery has exploded in recent years. It is allowing us to find new uses for old drugs. Here are three developments in the field worth looking out for:</p>
<h2>Patches instead of injections</h2>
<p>Sometimes a drug can only be given by injection. This can be impractical in many situations, such as when patients are in rural areas. </p>
<p>A way to avoid the needle is through the use of “patches” that deliver medicines through the skin. These patches have hundreds of tiny needles, which are used to “inject” medicines under the skin painlessly. This technology has been used to provide <a href="http://www.tevapharm.com/Pages/default.aspx">migraine treatment</a> and <a href="http://medcitynews.com/2013/05/its-smaller-than-a-fingernail-but-this-needle-free-nanopatch-could-be-the-future-of-vaccines">deliver vaccines</a>. It also has the big advantage of needing no specialised equipment or expertise, which means it can be administered by the patient directly. </p>
<h2>Ultrasound disruption</h2>
<p>In the treatment of neurological diseases, drugs have an extra hurdle to jump to be effective <a href="http://www.ncbi.nlm.nih.gov/pubmed/15207256">called the blood-brain-barrier</a> (BBB). The BBB regulates what substances are allowed to pass into the brain and, because of its selectivity, many drugs are unable to pass through. </p>
<p>Now researchers have used ultrasound – sound which has a much higher frequency than that humans can hear – to <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038976/">briefly disrupt the barrier</a> so as to allow the drug to pass through. This technique looks promising, with translation to human studies <a href="http://sunnybrook.ca/research/content/?page=sri-groups-fus-home">being carried out this year</a>, but the side-effects of temporarily opening the BBB are currently unknown.</p>
<h2>Drug vehicles</h2>
<p>Another form of drug delivery is one that is invisible to the naked eye. It happens deep within the body through “drug vehicles”. For instance, drugs that get quickly excreted from the body can be “hidden” using multiple layers of chemicals. This hiding is supposed to work until the target is reached, where the drug is released.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/61993/original/5p7k8hxx-1413472151.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/61993/original/5p7k8hxx-1413472151.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/61993/original/5p7k8hxx-1413472151.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/61993/original/5p7k8hxx-1413472151.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/61993/original/5p7k8hxx-1413472151.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/61993/original/5p7k8hxx-1413472151.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/61993/original/5p7k8hxx-1413472151.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Delivered in tiny packages.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/emsl/4606724422">emsl</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p>One way to hide drugs is through the use of <a href="http://www.nano.gov/nanotech-101/what/definition">nanotechnology</a>, which is the science of the small things (a nanometre is a billionth of a metre). Nanoscale materials have the advantage of being a similar size to biological molecules such as proteins and can, if designed correctly, evade detection and elimination by the immune system.</p>
<p>Metal nanoparticles are easy to make and tailor for different uses, they can also be designed so that once they reach the intended target, ultrasound can be used to break apart the <a href="http://www.academia.edu/1479004/Smart_Delivery_and_Controlled_Drug_Release_with_Gold_Nanoparticles_New_Frontiers_in_Nanomedicine">nanoparticle to release drugs</a>. They can also have other properties that can be combined with diagnostic and therapeutic tools. For example, iron oxide nanoparticles can be monitored inside the body using magnetic resonance imaging (MRI). However, some metallic nanoparticles often cannot be used in large doses because metals such as cadmium and gadolinium can have severe side-effects.</p>
<p>That is why non-metal nanoparticles, usually based on a polymeric structure, are of great interest. Take the example of delivering insulin. If consumed orally, in the form of tablets, insulin is degraded by bodily enzymes before it can be absorbed into the blood stream. That is why treatment of type-1 diabetes involves injection of insulin, regularly carried out by the patient themselves. Due to the inconvenience of this treatment along with potential side effects, researchers across the world are trying to <a href="http://www.ncbi.nlm.nih.gov/pubmed/23567010">overcome this problem</a>. There are many promising developments of enabling insulin delivery via biodegradable nanoparticles in tablet form, many of which are at different stages in clinical trials.</p>
<p>So while the researchers come up with solutions to developing new drugs, academia and industry are heavily investing in finding new ways of making old ones more effective. It is currently too early to tell if it will have a significant clinical benefit.</p><img src="https://counter.theconversation.com/content/33109/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Benjamin Burke does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Development of new drugs for treatment of disease is an expensive, time-consuming and labour-intensive effort for both pharmaceutical companies and academics. For the past 15 years, “cost per approval…Benjamin Burke, Molecular Imaging Post-Doctoral Research Assistant, University of HullLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/160542013-09-17T05:36:29Z2013-09-17T05:36:29ZNanotechnology in medicine isn’t just about size<figure><img src="https://images.theconversation.com/files/31269/original/z3nx2xpd-1379004905.jpg?ixlib=rb-1.1.0&rect=3%2C1%2C1020%2C682&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Many of the colours in medieval stained glass are produced by nanoparticles.</span> <span class="attribution"><span class="source">Quinn Anya</span></span></figcaption></figure><p>While scientists develop new drugs to treat a multitude of conditions, nanotechnology is pushing the boundaries of how we deliver them to patients - targeting delivery to cancer cells and giving a drug dose once a month rather than every day.</p>
<p>Using nano-sized carriers to deliver medicine has been around for some time. Nearly 20 years ago chemotherapy drug <a href="http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Chemotherapy/Individualdrugs/Liposomaldoxorubicin.aspx">liposomal doxorubicin</a> (brand name Doxil in the US) was approved for treating Kaposi’s sarcoma, a rare cancer often found in patients with AIDS. The molecules of the anti-cancer drug doxorubicin are held in a liposome, a fatty particle, that allows the nanomedicine to last longer in the body. And liposome technology has been available since the 1960s.</p>
<p>But nanotechnologies are continually evolving, as are their applications and the sophistication of treating and diagnosing disease.</p>
<h2>Solid or carrier</h2>
<p>In broad terms, nanotechnology in drug delivery involves either forming solid drug nanoparticles or loading the drug into nanocarriers that improve how a medicine is distributed in the body. One of the latest offerings is an experimental <a href="http://www.nanomagazine.co.uk/index.php?option=com_content&id=2254:injectable-smart-sponge-holds-promise-for-controlled-drug-delivery&catid=38:nano-news&Itemid=159">injectable “smart sponge”</a> that expands and contracts in response to blood sugar levels to release insulin within diabetic patients as needed. </p>
<p>Solid drug nanoparticles are typically made by taking large chunks of water-insoluble drugs and grinding them into particles with diameters measurable in 100s of nanometers, with each particle about one millionth the size of a tennis ball. There are now numerous examples of these formulations that have been licensed as safe and effective for treating diseases ranging from organ rejection, cholesterol reduction, schizophrenia, chronic pain and inflammation. </p>
<p>Until recently, the primary aim of solid drug nanoparticles was to improve the delivery of drugs taken by mouth; by increasing the amount of drug that is able to cross the intestinal barrier and enter the bloodstream. But recent work, in the area of HIV, has been about developing ways to take medicines less frequently - for example as little as once a month or even longer using a solid drug nanoparticle depot that is injected into muscle. This kind of work may make it easier for people with HIV to manage their treatment.</p>
<p>Recent <a href="https://news.liv.ac.uk/2012/08/30/researchers-pioneer-worlds-first-hivaids-nanomedicines/">work at Liverpool University</a> with solid drug nanoparticles could reduce the doses required for orally administered HIV drugs and Phase I clinical trials are now being planned.</p>
<h2>A less toxic payload</h2>
<p>Doxil is a nanocarrier-based medicine, where a particle of fat (a liposome) is the carrier. But there are a plethora of different nanocarriers at various stages of development. They range from various polymeric nanoparticles, nanoemulsions and inorganic materials such as gold or silver nanoparticles. </p>
<p>The majority of nanocarrier-based medicines are being developed to treat cancer and are generally injected directly into the blood. Their benefits stem from their ability to target certain areas of the body. By increasing the amount of drug at the target and reducing it in other tissues, these nanomedicines reduce the toxicity that occurs when the drug is more widely distributed in the body.</p>
<p>Almost all nanocarrier-based medicines in development involve either passive targeting or active targeting. In cancer, as solid tumours grow and expand they disrupt the tissue that surrounds them creating nano-sized pores that allow medicines like Doxil to leak through and penetrate the tumour. But in healthy tissue the barrier remains intact and prevents the accumulation of the nanocarrier. Imagine the tissue around the tumour is like a net while the tissue around healthy tissue is like a cloth. Both net and cloth will let water through (dissolved drug in a conventional form) but only the net (tumour) will let through sand (nanoparticles). </p>
<p>The ability to capitalise on an inherent process in this way is called passive targeting. And recent research into amplifying this passive targeting alongside active targeting has shown promising data. Usually, this involves modifying the nanoparticle surface to add a targeting ligand, a structure that can specifically recognise features of diseased cells. This specifically homes the medicine to the target cells. One of the <a href="http://www.marketwatch.com/story/bind-doses-first-patient-in-a-phase-2-clinical-study-of-bind-014-in-prostate-cancer-2013-08-19">first actively targeted nanomedicines</a>, BIND-014, recently entered into Phase II clinical trials. </p>
<p>Although most of these nanomedicines are used in cancer, other examples are being used to treat conditions from multiple sclerosis to infectious diseases. For example, Ambisome, another liposome-based medicine that contains the drug amphotericin B, is effective at eliminating fungal infections but is less toxic, again because of its favourable distribution in the body.</p>
<h2>Optical properties</h2>
<p>Nanoparticles have long been known to have optical properties. Many of the colours within medieval stained-glass windows were produced using nanoparticles of inorganic materials such as silver and gold. These nanoparticles are so small that they are able to interfere with the wavelength of the light that hits them due to a process we now know of as surface plasmon resonance. </p>
<p>The potential application of these optical properties for the diagnosis and monitoring of diseases have recently been attracting interest. For example, certain nanoparticles are able to selectively accumulate within tumours and the optical properties allow them to be seen using external equipment. </p>
<p>More recently, nanotheranostics (a combination of nano, therapy and diagnostics) have attracted attention for their potential to not only enable us to see disease tissue but to simultaneously deliver a drug payload. In cancer treatment this would allow doctors to treat patients and study the cancer at the same time.</p><img src="https://counter.theconversation.com/content/16054/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Owen is the co-inventor of patents related to HIV nanomedicines</span></em></p>While scientists develop new drugs to treat a multitude of conditions, nanotechnology is pushing the boundaries of how we deliver them to patients - targeting delivery to cancer cells and giving a drug…Andrew Owen, Molecular and Clinical Pharmacology, University of LiverpoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/70592012-07-08T20:45:44Z2012-07-08T20:45:44ZWhy some people ‘wake up’ during surgery<figure><img src="https://images.theconversation.com/files/12625/original/46mhjpq6-1341453220.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Around one in every 1,000 patients will recall sounds or senstations while under general anaesthetic.</span> <span class="attribution"><span class="source">nanda uforians</span></span></figcaption></figure><p>Awareness during general anaesthesia is very uncommon, but when it occurs it’s distressing for patients and their carers. Our understanding of this phenomenon has grown over the past decade but we’re still investigating why some people are more vulnerable than others. </p>
<p>General anaesthesia is intended to prevent all recall of events during surgery. It’s considered one of the top ten discoveries in medicine, along with vaccines and antibiotics, because of all the suffering that it’s prevented. </p>
<p>Other types of anaesthesia, such as regional and local anaesthesia (including epidurals and arm blocks) and sedation (or twilight sleep) are <em>not</em> intended to prevent recall of events – they’re designed to make the patient pain-free and, in the case of sedation, sleepy and relaxed.</p>
<p>Awareness during general anaesthesia is defined clinically as the “postoperative recall of intraoperative events”. Typically, the patient emerges from the anaesthetic and describes sounds, sensations and emotions from a time when they were supposed to be unconscious. Only some patients recall pain and most of the episodes are brief.</p>
<p>One patient, for example, remembered going off to sleep for a gall bladder operation and then recalled waking up and feeling a burning pain in her abdomen. She could hear her surgeon talking and the beeping of the anaesthetic monitors, but couldn’t move. A short time later she lost consciousness again.</p>
<p>Patients can also report dreaming during anaesthesia. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17197843">Our research</a> has shown that most dreaming is not related to excessively light anaesthesia or awareness. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/12642/original/gq2vdvr6-1341461806.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/12642/original/gq2vdvr6-1341461806.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/12642/original/gq2vdvr6-1341461806.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/12642/original/gq2vdvr6-1341461806.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/12642/original/gq2vdvr6-1341461806.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/12642/original/gq2vdvr6-1341461806.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/12642/original/gq2vdvr6-1341461806.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dreams during anaesthesia tend to be short and pleasant, often involving family and friends.</span>
<span class="attribution"><span class="source">JorgeMiente es</span></span>
</figcaption>
</figure>
<p>Typically, the dreams are short and pleasant, about family, friends, work and recreation. One patient, for instance, dreamt about being at work and talking with her colleagues as they prepared food; another remembered dreaming about playing with his grandchildren in the park.</p>
<p>Patients often forget that they had recalled a dream in the hours and days after surgery.</p>
<h2>How common is awareness?</h2>
<p>Awareness occurs in about one in every 1,000 patients having general anaesthesia. But some patients are at higher risk and some are at lower risk. Healthy, non-pregnant patients having routine elective surgery are at much lower risk (say, one in 10,000 patients). Sicker patients having bigger operations – especially emergency operations and open heart surgery – are at higher risk (up to one in 100). </p>
<p>Women having a caesarean section under general anaesthesia are also at high risk, because we want to avoid the depressant effects of general anaesthetics on the baby and therefore give a lower dose. </p>
<p>Anaesthetists don’t always find out about patients becoming aware while under anaesthesia, for a few reasons. One is that some patients are not distressed at all by the experience and don’t think to tell their anaesthetist. Others want to take time to be sure about whether they remember anything before they tell the doctors. </p>
<p>Still others go into a form of denial (called post-traumatic dissociation) – these patients are possibly at higher risk of developing post-traumatic stress disorder (PTSD). Our <a href="http://www.ncbi.nlm.nih.gov/pubmed/19861364">research has shown</a> that PTSD is unfortunately quite common after an episode of awareness, so we advocate referring these patients for psychological support right away.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/12641/original/wj5gmpdd-1341461534.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/12641/original/wj5gmpdd-1341461534.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/12641/original/wj5gmpdd-1341461534.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/12641/original/wj5gmpdd-1341461534.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/12641/original/wj5gmpdd-1341461534.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/12641/original/wj5gmpdd-1341461534.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/12641/original/wj5gmpdd-1341461534.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Patients who become aware during general anaesthesia are at risk of developing PTSD.</span>
<span class="attribution"><span class="source">Best In Plastics</span></span>
</figcaption>
</figure>
<h2>Causes of awareness</h2>
<p>Awareness occurs when the patient does not get enough anaesthetic drugs. Some awareness episodes are a result of problems with the equipment or delivery of the drugs, or mistakes made by the anaesthetist. </p>
<p>Other episodes are due to the fact that the patient is too sick to get much anaesthesia. General anaesthetic agents cause low blood pressure and a slow heart rate – this is a problem if the patient is also bleeding or has heart failure. </p>
<p>Finally, some patients seem to be resistant to general anaesthesia. Women wake up quicker from anaesthesia than men and this may be why they report more episodes of awareness.</p>
<h2>Prevention of awareness</h2>
<p>The first step in preventing awareness is acknowledging that it can occur. </p>
<p>As medical specialists in anaesthesia, our training includes checking the equipment and drugs, making a good plan for the patient, communicating that plan to the patient, keeping a keen eye on the patient (and the surgeon!) during the operation and making sure the patient wakes up pain free. We also have a good culture of reporting cases of awareness and discussing them at our regular quality assurance meetings.</p>
<p>New monitors of brain electrical activity (brain waves) can help as well. Our research project, <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2916300-9/abstract%20">the B-Aware Trial</a>, showed that a bispectral index (or BIS) monitor was able to prevent most cases of awareness in patients having high risk surgery. </p>
<p>The BIS monitor and other similar products are now widely used in Australia during general anaesthesia and the <a href="http://www.anzca.edu.au/">Australian and New Zealand College of Anaesthetists</a> recommends these monitors be available for all patients at high risk of awareness.</p>
<h2>The genetics of awareness</h2>
<p><a href="http://www.ncbi.nlm.nih.gov/pubmed/21918425">Genetic studies</a> have identified patients who are resistant, or very sensitive, to various drugs, because of their genetic makeup. </p>
<p>We’re interested to see whether we can find a gene that makes people more resistant to anaesthetics and therefore at higher risk of awareness. We wondered about this because some patients seem to remember things during what looks like a deep anaesthetic; some patients have more than one episode and there are some cases of mothers and daughters having awareness. </p>
<p>We’re seeking people who think that they were aware during a general anaesthetic (not a local anaesthetic or sedation) over the past 20 years. We intend to interview them and find out if they were aware during a full general anaesthetic. We’ll then take a mouth swab for DNA and do genetic tests. </p>
<p>If we can find a genetic link, then we may be able to prevent more cases of awareness.</p>
<p><em><strong>If you’re interested in participating in the study, ring 0413 295 122 (Australia) or 0212 280 085 (New Zealand).</strong></em></p><img src="https://counter.theconversation.com/content/7059/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kate Leslie receives funding from NHMRC and ANZCA</span></em></p>Awareness during general anaesthesia is very uncommon, but when it occurs it’s distressing for patients and their carers. Our understanding of this phenomenon has grown over the past decade but we’re still…Kate Leslie, Honorary professorial fellow, Department of Pharmacology, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.