MSGID: 1:317/3 642ba7df   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    New tech could deliver time-released drugs, vaccines for months    
      
     Date:   
         April 3, 2023   
     Source:   
         Rice University   
     Summary:   
         Bioengineers may have the prescription for a $100 billion global   
         problem: An innovative way to make time-released drugs could allow   
         patients to receive months-worth of medicines or vaccines in a   
         single shot.   
      
      
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   FULL STORY   
   ==========================================================================   
   Missing crucial doses of medicines and vaccines could become a thing of   
   the past thanks to Rice University bioengineers' next-level technology   
   for making time-released drugs.   
      
      
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   "This is a huge problem in the treatment of chronic disease," said Kevin   
   McHugh, corresponding author of a study about the technology published   
   online inAdvanced Materials. "It's estimated that 50% of people don't   
   take their medications correctly. With this, you'd give them one shot,   
   and they'd be all set for the next couple of months."  When patients   
   fail to take prescription medicine or take it incorrectly, the costs   
   can be staggering. The annual toll in the United States alone has been   
   estimated at more than 100,000 deaths, up to 25% of hospitalizations   
   and more than $100 billion in healthcare costs.   
      
   Encapsulating medicine in microparticles that dissolve and release drugs   
   over time isn't a new idea. But McHugh and graduate student Tyler Graf   
   used 21st- century methods to develop next-level encapsulation technology   
   that is far more versatile than its forerunners.   
      
   Dubbed PULSED (short for Particles Uniformly Liquified and Sealed to   
   Encapsulate Drugs), the technology employs high-resolution 3D printing   
   and soft lithography to produce arrays of more than 300 nontoxic,   
   biodegradable cylinders that are small enough to be injected with standard   
   hypodermic needles.   
      
   The cylinders are made of a polymer called PLGA that's widely used in   
   clinical medical treatment. McHugh and Graf demonstrated four methods   
   of loading the microcylinders with drugs, and showed they could tweak   
   the PLGA recipe to vary how quickly the particles dissolved and released   
   the drugs -- from as little as 10 days to almost five weeks. They also   
   developed a fast and easy method for sealing the cylinders, a critical   
   step to demonstrate the technology is both scalable and capable of   
   addressing a major hurdle in time-release drug delivery.   
      
   "The thing we're trying to overcome is 'first-order release,'" McHugh   
   said, referring to the uneven dosing that's characteristic with current   
   methods of drug encapsulation. "The common pattern is for a lot of the   
   drug to be released early, on day one. And then on day 10, you might   
   get 10 times less than you got on day one.   
      
   "If there's a huge therapeutic window, then releasing 10 times less on day   
   10 might still be OK, but that's rarely the case," McHugh said. "Most of   
   the time it's really problematic, either because the day-one dose brings   
   you close to toxicity or because getting 10 times less -- or even four or   
   five times less - - at later time points isn't enough to be effective."   
   In many cases, it would be ideal for patients to have the same amount   
   of a drug in their systems throughout treatment. McHugh said PULSED can   
   be tailored for that kind of release profile, and it also could be used   
   in other ways.   
      
   "Our motivation for this particular project actually came from the   
   vaccine space," he said. "In vaccination, you often need multiple doses   
   spread out over the course of months. That's really difficult to do in   
   low- and middle-income countries because of health care accessibility   
   issues. The idea was, 'What if we made particles that exhibit pulsatile   
   release?' And we hypothesized that this core-shell structure -- where   
   you'd have the vaccine in a pocket inside a biodegradable polymer   
   shell -- could both produce that kind of all-or-nothing release event   
   and provide a reliable way to set the delayed timing of the release."   
   Though PULSED hasn't yet been tested for months-long release delays,   
   McHugh said previous studies from other labs have shown PLGA capsules   
   can be formulated to release drugs as much as six months after injection.   
      
   In their study, Graf and McHugh showed they could make and load particles   
   with diameters ranging from 400 microns to 100 microns. McHugh said   
   this size enables particles to stay where they are injected until they   
   dissolve, which could be useful for delivering large or continuous doses   
   of one or more drugs at a specific location, like a cancerous tumor.   
      
   "For toxic cancer chemotherapies, you'd love to have the poison   
   concentrated in the tumor and not in the rest of the body," he   
   said. "People have done that experimentally, injecting soluble drugs   
   into tumors. But then the question is how long is it going to take for   
   that to diffuse out.   
      
   "Our microparticles will stay where you put them," McHugh said. "The   
   idea is to make chemotherapy more effective and reduce its side effects   
   by delivering a prolonged, concentrated dose of the drugs exactly where   
   they're needed."  The crucial discovery of the contactless sealing method   
   happened partly by chance. McHugh said previous studies had explored   
   the use of PLGA microparticles for time-released drug encapsulation,   
   but sealing large numbers of particles had proven so difficult that the   
   cost of production was considered impractical for many applications.   
      
   While exploring alternative sealing methods, Graf noticed that trying to   
   seal the microparticles by dipping them into different melted polymers   
   was not giving the desired outcome. "Eventually, I questioned whether   
   dipping the microparticles into a liquid polymer was even necessary,"   
   said Graf, who proceeded to suspend the PLGA microparticles above a hot   
   plate, enabling the top of the particles to melt and to self-seal while   
   the bottom of the particles remained intact, "Those first particle   
   batches barely sealed, but seeing the process was possible was very   
   exciting."Further optimization and experimentation resulted in consistent   
   and robust sealing of the cylinders, which eventually proved to be one of   
   the easier steps in making the time- released drug capsules. Each 22x14   
   array of cylinders was about the size of a postage stamp, and Graf made   
   them atop glass microscope slides.   
      
   After loading an array with drugs, Graf said he would suspend it about   
   a millimeter or so above the hot plate for a short time. "I'd just   
   flip it over and rest it on two other glass slides, one on either end,   
   and set a timer for however long it would take to seal. It just takes   
   a few seconds."  This work was supported by the Cancer Prevention   
   and Research Institute of Texas (RR190056), the National Institutes   
   of Health (EB031495, EB023833) and the National Science Foundation   
   (1842494, 2236422).   
      
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             o Health_&_Medicine   
                   # Pharmacology # Colon_Cancer # Alzheimer's_Research #   
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             o Matter_&_Energy   
                   # Physics # Quantum_Physics # Medical_Technology #   
                   Nanotechnology   
       * RELATED_TERMS   
             o Pharmaceutical_company o Anti-obesity_drug o Analgesic o   
             Delirium o H5N1 o Clinical_trial o Psychedelic_properties   
             o Antiretroviral_drug   
      
   ==========================================================================   
   Story Source: Materials provided by Rice_University. Original written   
   by Jade Boyd. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Tyler P. Graf, Sherry Yue Qiu, Dhruv Varshney, Mei‐Li   
      Laracuente,   
         Erin M. Euliano, Pujita Munnangi, Brett H. Pogostin, Tsvetelina   
         Baryakova, Arnav Garyali, Kevin J. McHugh. A Scalable Platform   
         for Fabricating Biodegradable Microparticles with Pulsatile Drug   
         Release.   
      
         Advanced Materials, 2023; DOI: 10.1002/adma.202300228   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/04/230403133524.htm   
      
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