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New Drug Delivery Method Developed by MIT Engineers
Engineers at MIT have introduced an innovative technique for administering certain medications in higher concentrations with reduced discomfort. This involves injecting medications as a suspension of microscopic crystals. When injected under the skin, these crystals form a drug “depot” that has the potential to sustain drug release for months or even years, minimizing the necessity for frequent injections.
This method holds promise for the administration of long-term contraceptives and other medications that require sustained dosage over extended durations. The drugs are prepared as a suspension, allowing for their delivery through a narrow needle, which tends to be more acceptable for patients.
“Our research indicates that we can achieve highly controlled and sustained drug release, potentially lasting several months and even years, all through the use of a small needle,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, who also practices as a gastroenterologist at Brigham and Women’s Hospital (BWH) and is a senior author of the study.
The paper, featured in Nature Chemical Engineering, lists former MIT and BWH postdoctoral fellow Vivian Feig, now an assistant professor of mechanical engineering at Stanford; MIT graduate student Sanghyun Park; and Pier Rivano, a former research scholar in Traverso’s lab, as lead authors.
Advancing Injection Methods
This research initiative was funded by the Gates Foundation with the aim of broadening contraceptive choices, especially in lower-income countries.
“Our primary objective is to offer women a variety of accessible and easy-to-administer contraceptive options that are practical for use in developing regions, with various durations of effectiveness,” explains Feig. “In this specific project, we aimed to merge the advantages of long-lasting implants with the simplicity of injectable options.”
Currently, there are injectable suspensions available in the U.S. and other markets, but these typically disperse throughout tissue post-injection, resulting in effective action lasting around three months. Alternative injectable formulations have been developed to create longer-lasting depots beneath the skin, but these often require significant quantities of precipitating polymers, making injections more complex and uncomfortable.
The team from MIT and BWH pursued a formulation intended for administration through a small-gauge needle that could last between six months and two years. They focused on the contraceptive drug levonorgestrel, a hydrophobic molecule capable of crystallization. The researchers found that suspending these crystals in a specific organic solvent resulted in the formation of a highly compact implant after injection, enabling the drug to be easily injected without relying on large amounts of polymer.
The solvent used, benzyl benzoate, is biocompatible and commonly utilized as an additive in injectable medicines. The team discovered that its poor solubility in biological fluids is what facilitates the solid drug crystals’ self-assembly into a depot once injected.
“The key advantage of the solvent is that it allows for injection through a fine needle, but once in the body, it enables the crystals to aggregate into a depot,” states Traverso.
Researchers can adjust the depot’s density to control the release rate of drug molecules into the body. They demonstrated that by incorporating small amounts of biodegradable polymers, specifically polycaprolactone, they could effectively modulate drug release duration while preserving the ease of injection.
“Incorporating a minute quantity of polymers—less than 1.6 percent by weight—allows us to adjust the drug release rate, thereby extending its effectiveness while maintaining injectability. This illustrates the adaptability of our system, which can be engineered for various contraceptive needs and customized dosing schedules for different therapeutic uses,” asserts Park.
Durable Drug Depots
The team validated their method by injecting the drug solution subcutaneously in rats, confirming that the drug depots remained stable and released the drug gradually over a three-month period. By the conclusion of the study, approximately 85 percent of the drug remained encapsulated in the depots, indicating the potential for prolonged drug release.
“We hypothesize that these depots could persist for over a year based on our analysis of preclinical data. Additional follow-up studies are in progress to further substantiate their effectiveness beyond our initial findings,” says Park.
Once established, the drug depots are compact enough to be surgically removed if necessary, enabling treatment cessation before complete drug administration.
This novel delivery system could also be adapted for medications targeting neuropsychiatric disorders, as well as treatments for HIV and tuberculosis. The research team is now advancing towards human trials by performing comprehensive preclinical studies to assess self-assembly under conditions more closely resembling clinical environments. “Our system is straightforward, essentially comprising a solvent, the drug, and a minimal addition of bioresorbable polymer. We are now contemplating future applications: Should we focus on contraception or explore other uses? These questions mark the next steps toward practical human applications,” states Traverso.
The research received funding from various organizations, including the Gates Foundation, the Karl van Tassel Career Development Professorship, the MIT Department of Mechanical Engineering, as well as several fellowships and grants dedicated to advancing scientific research.
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