An injectable soft implant for long-acting, reversible, ultra-stable release of therapeutics

Stevens, M. M.; Kütahya, C.; Panariello, L.; Najer, A.; Rizou, T.; Shamsabadi, A.; Brachi, G.; Peeler, D. J.; Zharova, L.; Fernandez Debets, T. F. F.; Peschke, P.; Constantinou, A. P.; Xie, R.; Cheng, Y.; Burdis, R.; Suarez-Bonnet, A.; Cihova, M.; Yeow, J.; Schaufelberger, F.; Malanchi, I.

doi:10.64898/2026.02.25.707913

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bioRxiv · 10.64898/2026.02.25.707913

An injectable soft implant for long-acting, reversible, ultra-stable release of therapeutics

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Abstract

Providing long-term (>6 months) zero-order drug release from easily administered formulations is a key challenge in improving patient adherence and facilitating access. Herein, we report the design and development of an injectable, biodegradable, long-acting polymeric microparticle-embedded hydrogel platform for prolonged, zero-order release of therapeutics. This "soft implant" is injectable for ease of administration and can be retrieved via a small incision, allowing for discontinuation of therapy if desired. Central to the platform are surface-eroding poly(orthoester) (POE) microparticles, which were molecularly tailored to tune zero-order drug release across a wide range of timeframes. We demonstrate the clinical potential of the "soft implant" using levonorgestrel, a contraceptive agent requiring sustained dosing. In vitro, we observed zero-order release for 300 days, projected for >12 months, with behavior consistent with surface erosion further supported through Raman chemical mapping. In vivo studies confirmed zero-order release for six months, projected to 12 months, from a subcutaneous injection in rats. We envision that our platform could transform therapies that require long-term, regular drug dosing, significantly improving compliance and therapy outcomes.

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Stevens, M. M., Kütahya, C., Panariello, L., Najer, A., Rizou, T., Shamsabadi, A., Brachi, G., Peeler, D. J., Zharova, L., Fernandez Debets, T. F. F., Peschke, P., Constantinou, A. P., Xie, R., Cheng, Y., Burdis, R., Suarez-Bonnet, A., Cihova, M., Yeow, J., Schaufelberger, F., Malanchi, I.. 2026-02-26. An injectable soft implant for long-acting, reversible, ultra-stable release of therapeutics. https://doi.org/10.64898/2026.02.25.707913

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