Today, they use lab robots to fill the capsules, and they’re working to automate the entire process, which they call Pulsed, for particles that are uniformly liquefied and sealed to encapsulate drugs. McHugh believes this automation saves costs and makes the technology scalable. Thanks to minor adjustments to the capsule’s recipe, the pulsed particles rupture with clear, predictable delays ranging from days to more than a month.
For their recent study, their team wanted to know how quickly these capsules would break down in a living animal, so they compared the timing in test tubes to that in mice. In one trial, they loaded the microparticles with small fluorescent molecules instead of drugs. With the mice, they injected a small volume of the capsules under the animals’ skin, then monitored the fluorescence as the molecules diffused out. With the test tubes, they kept the capsules in a saline solution at body temperature and monitored when the fluorescent molecules entered the solution. In all cases, the timing matched. This means that timing predictions based on lab experiments are likely to hold up well in living bodies.
They also tested whether the microparticles can carry biological substances without spoiling them. They tested one — bevacizumab, the antibody that treats macular degeneration and some cancers — by loading the drug into microparticles along with a cocktail of stabilizing chemicals. Eighteen days later, the drug remained more than 90 percent active.
The team envisions designing a library of these particles that can mimic different dosing schedules: daily, weekly, monthly or anything in between, depending on the patient. For example, while they haven’t yet tested their system with Covid vaccines, the capsules described in the new study may match the timing needed for them: two doses given three or four weeks apart.
“It’s a really important direction for the future of controlled and sustained 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 that the current particles are not ideal for drugs that need to be dosed several times a day – they don’t dissolve fast enough.
Compared to other injectables or delayed-release oral pills, the microparticle results are “very exciting,” said Rahima Benhabbour, a polymer chemist at the University of North Carolina who is not involved with McHugh’s team. “The main takeaway here is the stability of the biologics. I Real liked that,” she says.
Benhabbour’s team uses PLGA to create implants that release drugs slowly and steadily, with no initial burst. (Drug levels from injections usually peak before declining.) That’s essential for HIV pre-exposure prophylaxis, or PrEP, which requires a person to maintain a certain concentration of the drug in their bloodstream at all times to be protected. Her team has published a newspaper in February reported that, based on tests in macaque monkeys, their implants could maintain those PrEP concentrations in humans for more than five months.
Benhabbour warns that it’s unclear how many microparticles can be squeezed into one injection. The maximum volume for subcutaneous injections for humans (such as those given to McHugh’s mice) is 1.5 milliliters. That’s not guaranteed to have enough room for multiple doses, especially for drugs like PrEP that require a lot of medication per dose. “The only question I have is: Can they deliver enough??” she says.