Microneedle Technology Offers Promising Nonsurgical Delivery for Long-Acting Contraceptives: Study
USA: A new study published in Nature Chemical Engineering on March 24, 2025, reveals that a novel microneedle-based method for delivering the long-acting contraceptive levonorgestrel (LNG) could provide a more accessible, nonsurgical alternative for women. If successful in humans, this technology could also be adapted for other long-acting therapeutics, improving treatment accessibility and adherence.
Injectable drug depots have significantly enhanced medication adherence by simplifying dosing. A key consideration for patient acceptance of injectables is the comfort level with needle injections, with the needle gauge playing a crucial role in discomfort. By maximizing drug loading in injectables, it is possible to achieve longer drug release while minimizing both injection volume and patient discomfort.
To address these needs, Dr. Vivian R. Feig and her team from the Department of Mechanical Engineering at Stanford University developed the Self-Aggregating Long-Acting Injectable Microcrystals (SLIM). This innovative formulation contains drug microcrystals that self-aggregate in the subcutaneous space, forming a monolithic implant with a low polymer-to-drug ratio (0.0625:1 w/w). By reducing the amount of polymer in the formulation, SLIM allows for injection through smaller, low-profile needles (less than 25G) while maintaining a high drug concentration (293 mg/ml).
In both in vitro and in vivo studies, Dr. Feig’s team demonstrated that self-aggregation occurs due to solvent exchange at the injection site. Slower solvent exchange leads to more compact microcrystals and lower porosity in the implant. The study also showed that this self-aggregation process promotes longer drug release in rodents. The team believes that SLIM has the potential to provide cost-effective solutions, particularly for contraceptive treatments.
The SLIM system, using LNG as a proof-of-concept, is designed to enable slow drug release through the self-aggregation of drug crystals at the injection site. The study found that the rate of solvent exchange plays a critical role in the structure and release dynamics of the drug depot. Slower solvent exchange results in more compact microcrystals and a slower drug release. SLIM can be injected through needles as small as 30G, offering a significant advantage over aqueous suspensions. In vivo testing confirmed the system’s safety and efficacy, showing prolonged drug release with minimal side effects.
Dr. Feig and her colleagues suggest that SLIM could revolutionize contraceptive technology by reducing the frequency of administration compared to current options like Depo-Provera and Sayana Press. Future research will focus on optimizing SLIM’s dosage, release kinetics, and clinical applications, with the potential to expand the technology for other drug treatments.
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. https://doi.org/10.1038/s44286-025-00194-x
