Researchers from Massachusetts Institute of Technology have invented a method to generate drug-ferrying particles that can deliver multiple doses of a vaccine over an extended length of time with just one injection.
The particles, made from a biocompatible, FDA-approved polymer, look like tiny coffee cups that can be filled with a drug and sealed. The polymer is designed to degrade at certain times, spilling the cup and releasing its contents.
The team’s work was published this week in Science.
“We are very excited about this work because, for the first time, we can create a library of tiny, encased vaccine particles, each programmed to release at a precise, predictable time, so that people could potentially receive a single injection that, in effect, would have multiple boosters already built into it,” senior author Robert Langer, MIT’s David H. Koch Institute professor, said in prepared remarks. “This could have a significant impact on patients everywhere, especially in the developing world where patient compliance is particularly poor,”
The team started working to develop these drug-delivering particles as a part of an effort supported by the Bill & Melinda Gates Foundation. The project was hoping to find a way to deliver many doses of a vaccine over a period of time with a single injection. Young children in developing countries may not get to see a doctor frequently, so this one-time injection technology could allow them to get all of the vaccines they would need during the first years of life.
The researchers developed a sealable cup made from PLGA – a polymer that is already used in medical devices like implants and sutures, and can be designed to degrade at certain rates.
They were unable to use conventional 3D printing to create the cups, so they invented a new technique. They used photolithography to create silicon molds for the cups and lids. Once the PLGA cups were formed, the team used a custom dispensing system to fill each cup with a vaccine. Then the lids were aligned and fused onto the cup to seal the drug inside.
“Each layer is first fabricated on its own, and then they’re assembled together,” senior author Ana Jaklenec said. “Part of the novelty is really in how we align and seal the layers. In doing so we developed a new method that can make structures which current 3-D printing methods cannot. This new method called SEAL (StampEd Assembly of polymer Layers) can be used with any thermoplastic material and allows for fabrication of microstructures with complex geometries that could have broad applications, including injectable pulsatile drug delivery, pH sensors, and 3-D microfluidic devices.”
The molecular weight of the polymer, as well as the structure of the polymer molecules, decides how fast the particles degrade following administration, according to the team.
Injecting many particles that degrade at different rates essentially mimics the effect of a vaccine schedule, creating bursts of drug at a predetermined time.
“In the developing world, that might be the difference between not getting vaccinated and receiving all of your vaccines in one shot,” lead author Kevin McHugh said.
The drug-delivery technique was successful in mice at 9, 20 and 41 days following injection, the team reported. The researchers also tested particles filled with a protein called ovalbumin, which triggers an immune response.
The team found that one injection of the particles induced a strong immune response – it was even comparable to a response triggered by two conventional injections with twice the dose.
“The SEAL technique could provide a new platform that can create nearly any tiny, fillable object with nearly any material, which could provide unprecedented opportunities in manufacturing in medicine and other areas,” Langer said.