Exercise-Induced Stimulation of Self-Powered Nanofibers for Aspirin/Lysine Delivery in the Prevention of Denervated Muscle Atrophy.

Abstract

Denervation-induced muscle atrophy causes a 40-50% reduction in muscle fiber size within 2 weeks. This negatively impacts muscle quality and function. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce muscle atrophy by 20%. However, their bioavailability and gastrointestinal side effects raise concerns. Furthermore, multiple intramuscular injections can be difficult for patients. This is due to tolerance issues and discomfort from high doses. Muscle-targeted sustained-release delivery offers a solution by avoiding gastrointestinal problems and first-pass effects. Here, we present a self-powered gelatin nanofiber membrane (NFM) designed for the sustained release of aspirin/lysine (one NSAID). This method eliminates the need for repeated injections and directly targets inflammatory factors and superoxide in denervated muscles. As a result, it leads to a 44% increase in muscle weight and improved functional capacity in daily movements. Although the NFM requires implantation, its self-powered stimulation promotes muscle quality and enhances further drug release. Additionally, exercise-induced stimulation can intelligently control drug delivery through the self-powered nanofibers. Transcriptomic studies have confirmed that the NFM regulated muscle angiogenesis <i>via</i> inhibiting renin-angiotensin signal. Furthermore, its anti-inflammatory and antioxidant effects were enhanced with the incorporation of aspirin/lysine.