MIT engineers have developed a groundbreaking injectable drug delivery system that could dramatically reduce the frequency and discomfort of injections for patients requiring long-term medication. The innovation uses crystal suspensions that, once injected, form a long-lasting "depot" under the skin capable of releasing medication consistently over months or potentially years.
Self-Assembling Drug Depot Technology
The novel approach involves suspending drug crystals in a biocompatible benzyl benzoate solvent that allows for injection through a thin needle. Once under the skin, the crystals self-assemble into a compact depot that serves as a medication reservoir, gradually releasing the drug over extended periods.
"We showed that we can have very controlled, sustained delivery, likely for multiple months and even years through a small needle," said Giovanni Traverso, an associate professor of mechanical engineering at MIT who led the research.
The key innovation lies in the solvent's inability to mix with bodily fluids, which causes the drug crystals to clump together after injection, forming the depot. This property enables easier administration through smaller needles while maintaining long-term efficacy.
"The solvent is critical because it allows you to inject the fluid through a small needle, but once in place, the crystals self-assemble into a drug depot," Traverso explained.
Tunable Drug Release Mechanism
One of the system's most significant advantages is the ability to control medication release rates by adjusting the depot's density. Researchers demonstrated this capability by incorporating small amounts of polycaprolactone, a biodegradable polymer, into the formulation.
"By incorporating a very small amount of polymers — less than 1.6 percent by weight — we can modulate the drug release rate, extending its duration while maintaining injectability," said Sanghyun Park, an MIT graduate student involved in the research. "This demonstrates the tunability of our system, which can be engineered to accommodate a broader range of contraceptive needs as well as tailored dosing regimens for other therapeutic applications."
This tunability represents a significant improvement over existing injectable suspensions, which are typically short-acting, or long-lasting injectable depots that require high concentrations of polymers, making them difficult and painful to administer.
Promising Preclinical Results
In rat studies, the injected drug depots remained stable and released medication steadily for three months. With approximately 85% of the drug still remaining after this period, researchers project the depots could potentially provide effective treatment for significantly longer durations.
"We anticipate that the depots could last for more than a year, based on our post-analysis of preclinical data. Follow-up studies are underway to further validate their efficacy beyond this initial proof-of-concept," Park noted.
If necessary, these compact drug depots can be surgically extracted to halt treatment before complete drug depletion, offering additional flexibility for patient care.
Contraceptive Applications and Beyond
The research, funded by the Gates Foundation, initially focused on developing improved contraceptive options for women, particularly in developing nations. The team used levonorgestrel, a crystal-forming contraceptive, as their model drug for the system.
However, the potential applications extend far beyond contraception. Researchers believe this drug delivery method could transform treatment approaches for various conditions, including neuropsychiatric disorders, HIV, and tuberculosis—all conditions that benefit from consistent medication levels over extended periods.
Addressing Global Healthcare Challenges
This innovation addresses several critical healthcare challenges, particularly in resource-limited settings. By reducing the frequency of injections, the system could improve patient compliance, decrease healthcare costs, and minimize the logistical burdens associated with regular medication administration.
The simplicity of the system—relying on a combination of solvent, drug, and minimal biodegradable polymer—makes it particularly promising for widespread implementation across various medical treatments.
Next Steps Toward Clinical Application
The MIT team is now conducting further preclinical studies to prepare for human trials, with a focus on understanding how the drug depot assembles and functions in realistic skin conditions. These studies will help determine the system's safety profile and efficacy in humans.
If successful in clinical trials, this injectable drug depot technology could revolutionize long-term treatment approaches across multiple therapeutic areas, offering patients the possibility of years of consistent medication with minimal interventions.
