MIT engineers have developed a novel method for delivering certain drugs in higher doses with minimal discomfort by injecting them as a suspension of tiny crystals. Once beneath the skin, these crystals self-assemble into a long-lasting drug "depot," potentially eliminating the need for frequent injections by sustaining drug release for months or even years.

This innovative approach holds promise for long-term contraceptive delivery and other extended-release medications. Since the drugs are injected as a suspension, they can be administered through a narrow needle, making the process more tolerable for patients.

“We demonstrated the ability to achieve highly controlled, sustained drug delivery—likely spanning multiple months to even years—via a small-gauge needle,” says Giovanni Traverso, associate professor of mechanical engineering at MIT, gastroenterologist at Brigham and Women’s Hospital (BWH), associate member of the Broad Institute, and senior author of the study.

The research, published in Nature Chemical Engineering, is led by former MIT and BWH postdoc Vivian Feig (now an assistant professor at Stanford University), MIT graduate student Sanghyun Park, and Pier Rivano, a former visiting research scholar in Traverso’s lab.

Easier Injections
The project originated from a Gates Foundation initiative aimed at expanding contraceptive options, particularly in developing regions.

“Our goal is to offer women a variety of contraceptive formats that are easy to use, suited for developing countries, and available in different durations,” says Feig. “We sought to merge the benefits of long-acting implants with the simplicity of self-administered injectables.”

While injectable drug suspensions exist, they typically disperse throughout the tissue post-injection, limiting their effectiveness to about three months. Other long-lasting injectable products require large amounts of polymers (23–98% of the formulation by weight), making them harder to inject.

To overcome these limitations, the MIT and BWH team aimed to create a formulation that could be administered via a small needle and last between six months and two years. They focused on levonorgestrel, a hydrophobic contraceptive drug capable of forming crystals. By suspending these crystals in a specific organic solvent, they discovered that the crystals self-assembled into a compact depot after injection—without requiring large amounts of polymer—ensuring both injectability and extended drug release.

The solvent, benzyl benzoate, is biocompatible and has been previously used in injectable drugs. The researchers found that its poor miscibility with biological fluids enables the drug crystals to self-organize into a stable depot under the skin.

“The solvent is crucial because it allows the fluid to pass through a small needle while enabling the crystals to self-assemble into a drug depot once injected,” Traverso explains.

By adjusting the density of the depot, the researchers can control the rate at which the drug is released into the body. Adding small amounts of polycaprolactone, a biodegradable polyester, allows for precise modulation of drug release duration.

“With just a minimal amount of polymer—less than 1.6% by weight—we can fine-tune drug release while preserving injectability. This flexibility makes our system adaptable to a wide range of contraceptive and therapeutic needs,” says Park.

Stable Drug Depots
The team tested their method by injecting the drug formulation subcutaneously in rats. The results showed that the depots remained stable and steadily released the drug over three months. At the end of the study, approximately 85% of the drug was still retained, suggesting the potential for much longer-lasting drug release.

“We estimate these depots could last over a year based on our preclinical data, and we’re conducting further studies to confirm their long-term efficacy,” says Park.

Additionally, once formed, the depots remain compact enough to be surgically removed if needed, allowing for early discontinuation of treatment.

Beyond contraception, this technique could be applied to medications for neuropsychiatric disorders, HIV, and tuberculosis. The researchers are now conducting advanced preclinical studies to assess the technology in a more clinically relevant skin environment.

“This system is remarkably simple—it consists of a solvent, the drug, and a small amount of bioresorbable polymer,” Traverso notes. “Now, we’re exploring which applications to prioritize, whether it’s contraception or other therapeutic areas, as we move toward human trials.”

The research was supported by the Gates Foundation, the Karl van Tassel Career Development Professorship, the MIT Department of Mechanical Engineering, a Schmidt Science Fellows postdoctoral fellowship, the Rhodes Trust, a Takeda Fellowship, a Warren M. Rohsenow Fellowship, and a Kwangjeong Educational Foundation Fellowship.

Source: https://news.mit.edu/2025/engineers-develop-better-way-to-deliver-long-lasting-drugs-0324