Bioengineers at Rice University developed a new technology for delivering drugs in a time-releasing manner.
Kevin McHugh, corresponding author of a study about the technology, believes this could make missing doses of medicines and vaccines a thing of the past. McHugh and the Rice team saw their work published online in Advanced Materials.
According to McHugh and graduate student Tyler Graf, encapsulating medicine in microparticles that dissolve and release drugs over time isn’t new. However, they believe their method — using 21st century methods to develop next-level encapsulation technology —offers more versatility in medication delivery.
“This is a huge problem in the treatment of chronic disease,” McHugh said in a post on Rice’s website. “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.”
About the microcylinder technology for drug delivery
McHugh and Graf’s team named the technology PULSED, short for particles uniformly liquified and sealed to encapsulate drugs. It employs high-resolution 3D printing and soft lithography to produce arrays of more than 300 nontoxic, biodegradable cylinders. These are small enough for injection with standard hypodermic needles.
A polymer called PLGA, commonly used in medical treatments, comprises the cylinders. McHugh and Graf demonstrated four methods of loading the microcylinders with drugs, tweaking the PLGA recipe. This varies how quickly the particles dissolve and release the drugs. They observed time frames from as little as 10 days to as long as nearly five weeks. Researchers also found a fast and easy way to seal the cylinders. This provides assurances of scalability and capability in time-release drug delivery.
“The thing we’re trying to overcome is ‘first-order release,’” McHugh said. “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.
“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.”
The researchers can also tailor PULSED for a release profile that offers the same amount of drug throughout treatment. McHugh says it can be used in other ways, too.
“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 healthcare 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.”
Proving that it works
The team has not yet tested the technology for months-long release delays. However, McHugh said other labs’ studies showed formulations that release drugs as far as six months post-injection.
Graf and McHugh demonstrated particle loads ranging from 400 microns to 100 microns in their study. They believe this size enables particles to stay where injected until they dissolve. That could aid in delivering large or continuous doses of one or more drugs at a specific location,. They gave an example of 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,” McHugh 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. 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 team tried to seal microparticles by dipping them into different melted polymers. However, this failed to provide the desired outcome. Eventually, they determined that suspending the PLGA microparticles above a hot plate enabled the top of the particles to melt. This resulted in a “self-seal” while the bottom of the particles remained intact.
After loading an array with drugs, Graf suspended it about a millimeter above the hot plate for a short time. The sealing process just took a few seconds, he said.
