Monolithic Shape-Shifting Absorbable Implants for Long-Term Contraception

Li, J.; Clark, B. G.; Khosravi, P.; Cotter, C.; Liang, J. Y.; Ling, S. R.; Su, Y.; Qi, K. J.; Codreanu, F.; D'Orio, E.; Tan, I. T.; Green, J. E.; Murawska, K.; Lopes, A.; Muller, B. N.; Hayward, A. M.; Fabian, N.; Pettinari, A.; Schmidt, K.; Laidlaw, B.; Platero, M.; Guevara, A.; Bernstock, J. D.; Owyang, S. Y.; Chai, P. R.; Langer, R.; Traverso, G.

doi:10.1101/2025.05.18.654764

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bioRxiv · 10.1101/2025.05.18.654764

Monolithic Shape-Shifting Absorbable Implants for Long-Term Contraception

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Abstract

Reversible contraceptives empower women to prevent unintended pregnancies and enable family planning. However, the need for frequent dosing with pills or injections often leads to suboptimal medication adherence and reduced effectiveness-an issue common to many chronic conditions. Long-acting drug delivery implants offer a compelling alternative by enabling autonomous, multi-year drug release, thereby improving real-world adherence and treatment outcomes. However, user acceptability and access are limited by need for invasive insertion and surgical end-of-life removal, particularly in low-resource settings, as well as by limited drug loading and suboptimal drug utilization efficiency, which constrain both the duration of therapy and the range of drugs that can be effectively delivered. To address these limitations, we developed the Monolithic Shape-shifting Absorbable Implants for Chronic Care (MoSAIC) platform-a minimally invasive, fully bioresorbable system that integrates compacted drug formulations with a space-efficient device architecture. This approach reduces implant size, eliminates the need for surgical removal, and prolongs therapeutic duration compared to existing implants. We develop compacted formulations of the contraceptive drug levonorgestrel (LNG), and other poorly water-solubility drugs, demonstrating exceptional drug loading (100% w/w) and multi-year sustained drug release via surface-mediated dissolution in rats. When incorporated into MoSAIC devices, these formulations enable high-efficiency drug loading and zero-order drug release kinetics with geometrically tunable rates and durations. As a result, MoSAIC systems can be designed to be smaller, less invasive, and/or longer lasting than current contraceptive implants such as Jadelle(R) and Nexplanon(R). The MoSAIC platform expands access to reversible contraception and supports long-term medication adherence, with the potential to improve health outcomes and quality of life. More broadly, it provides a flexible approach for delivering other potent, low-solubility therapeutics and lays the foundation for a "dose it and forget it" paradigm in chronic disease management, where adherence is designed into the therapy itself.

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Li, J., Clark, B. G., Khosravi, P., Cotter, C., Liang, J. Y., Ling, S. R., Su, Y., Qi, K. J., Codreanu, F., D'Orio, E., Tan, I. T., Green, J. E., Murawska, K., Lopes, A., Muller, B. N., Hayward, A. M., Fabian, N., Pettinari, A., Schmidt, K., Laidlaw, B., Platero, M., Guevara, A., Bernstock, J. D., Owyang, S. Y., Chai, P. R., Langer, R., Traverso, G.. 2025-05-23. Monolithic Shape-Shifting Absorbable Implants for Long-Term Contraception. https://doi.org/10.1101/2025.05.18.654764

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