Today, they use lab robots to fill the capsules, and they’re working to automate a whole process they call Pulsed, for liquefied and sealed granules homogenously closed. medicine package. McHugh believes this automation will cut costs and make the technology scalable. Thanks to small tweaks to the capsule formulation, Pulsed particles break apart with a pronounced, predictable delay ranging from a few days to more than a month.
For the recent study, their team wanted to know how quickly these capsules would break down in live animals, so they compared the time in the test tube to the time in mice. In one experiment, they loaded the microparticles with small fluorescent molecules instead of drugs. With mice, they injected a small amount of the capsule beneath the animal’s skin, then they watched for fluorescence as the molecules diffused outward. With test tubes, they kept the capsules in saline solution at body temperature and checked to see when the fluorescent molecules spilled into the solution. In any case, the timing is right. This means that time predictions based on laboratory experiments are likely to hold up well in living organisms.
They also tested whether the microparticles could carry biological substances without damaging them. They tested one – bevacizumab, an antibody that treats macular degeneration and some cancers – by loading the drug into microparticles with a stable mix of chemicals. Eighteen days later, the drug is still more than 90 percent active.
The team plans to design a library of these particles that can mimic different dosing schedules: daily, weekly, monthly, or something in between, depending on the patient. For example, although they have not yet tested their system with a Covid vaccine, the capsules described in the new study could fit the time it takes for them: two doses administered three or four times apart. week.
“It’s really an important direction for the future of controlled and sustainable drug delivery,” said Kibret Mequanint, a biomedical engineer at the University of Western Ontario who was not involved in the work. However, he points out, the existing granules aren’t ideal for drugs that require multiple daily dosing—they don’t dissolve quickly enough.
Rahima Benhabbour, a polymer chemist at the University of North Carolina who was not part of McHugh’s team, said that compared with other slow-release injectables or oral medications, the microparticle results were “very exciting.” “The main point here is biological stability. I Actually love that,” she said.
Benhabbour’s team uses PLGA to create implant drug release at a slow and steady rate, without an initial burst. (The drug concentration from the injections often spikes before tapering off.) It is necessary for HIV pre-exposure prophylaxis, or PrEP, which requires a person to maintain a certain level of drug in their blood at all times in order to be protected. Her team published a piece of paper in February reported that, based on tests on monkeys, their implant was able to maintain that level of PrEP in humans for more than 5 months.
Benhabbour cautions that it’s unclear how many microparticles can be squeezed into a single injection. The maximum volume for subcutaneous injection in humans (such as McHugh’s mouse injection) is 1.5 ml. That doesn’t guarantee enough space for multiple doses, especially drugs like PrEP that require multiple drugs per dose. “My only question is: Can they provide enough??” she speaks.
