Injectable drug depots simplify dosing schedules and improve medication adherence. Thinner needles make injections more comfortable, and higher drug concentrations allow for longer release times, smaller injection volumes, and better patient experience.
MIT researchers have devised a way to deliver drugs in higher concentration with less pain. They injected the drug as a suspension of tiny crystals. After penetrating the skin, the crystals assemble into a drug “depot” that could last for months or years.
The approach will eliminate repeated drug injections, especially for delivering long-lasting contraceptives or other drugs that need to be given for extended periods.
Dispersing drugs in suspension before injection offers key advantages for patient comfort. This approach allows the use of a narrow, fine-gauge needle, which minimizes discomfort and makes the process easier and more tolerable for patients.
Such needles are less invasive and cause minimal discomfort, making them more tolerable for patients, especially those sensitive to injections or requiring frequent doses.
This project aims to give women access to many different contraceptive formats that are easy to administer, compatible with being used in the developing world, and have various timeframes of durations of action. Researchers were interested in combining the benefits of long-acting implants with the ease of self-administrable injectables.
Other commercial injectable suspensions are dispersed throughout the tissue after injection and have limited lasting. Some of them require additional precipitating polymers, making drug injectability more difficult.
This study aimed to innovate long-lasting drug delivery with minimal patient discomfort. The researchers focused on levonorgestrel, a hydrophobic contraceptive drug known for its ability to form crystals.
By suspending these drug crystals in benzyl benzoate – a biocompatible organic solvent – they discovered a unique phenomenon: after injection, the solvent’s limited miscibility with biological fluids encouraged the drug crystals to self-assemble into a compact depot under the skin.
This method eliminates polymers required to form drug depots. As a result, the formulation remained compatible with narrow-gauge needles, making the injection process more tolerable for patients.
The innovative approach simplifies drug delivery and promises an extended-release period, lasting from six months to as long as two years. This could revolutionize treatments requiring long-term dosage maintenance.
Giovanni Traverso, an associate professor of mechanical engineering at MIT, said, “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.”
Researchers found that by adjusting the density of the depot, they could control how quickly the drug is released into the body. They added small amounts of polycaprolactone, a safe, biodegradable material, to the depot. This approach helps customize drug delivery for better treatment results.
The researchers discovered that they could precisely control how quickly the drug is released by adjusting the density of the depot. Adding less than 1.6% of a biodegradable polymer like polycaprolactone successfully modulated the release rate, extending the drug’s duration while preserving its ability to be injected through a narrow needle.
Contraceptive pills increase women’s risk of depression
This tunable system is very flexible, making it adaptable not only to varying contraceptive needs but also to customized dosing schedules in other medical treatments.
Researchers tested their method by injecting the drug solution into rats and found that the depots remained stable, gradually releasing the drug over three months. After this period, 85% of the drug was still in the depots, suggesting they could provide even longer release times—possibly over a year, as ongoing studies aim to confirm.
These depots can also be surgically removed if treatment needs to stop early. The approach shows potential for delivering drugs for neuropsychiatric conditions, HIV, and tuberculosis.
Researchers are now advancing preclinical tests to assess its application in humans and explore suitable medical uses, including contraception and other therapies. The system is simple, relying on a drug, solvent, and small amounts of biodegradable polymer, providing flexibility for various treatments.
Journal Reference
- Feig, V. R., Park, S., Rivano, P. G., Kim, J., Muller, B., Patel, A., Dial, C., Gonzalez, S., Carlisle, H., Codreanu, F., Lopes, A., Erdogan, A. E., Fabian, N., Guevara, A., Pettinari, A., Li, J., Liang, J., Liu, G. W., Tibbitt, M. W., . . . Traverso, G. (2025). Self-aggregating long-acting injectable microcrystals. Nature Chemical Engineering, 2 (3), 209-219. DOI: 10.1038/s44286-025-00194-x
Source: Tech Explorist
