Microneedle patch–based delivery of Pyr-Apelin-13 reverses functional and structural deficits in age-related sarcopenia

Abstract

Abstract Sarcopenia, the age-associated loss of skeletal muscle mass and function, currently lacks effective pharmacological interventions. Pyr-Apelin-13, a potent endogenous peptide that stimulates mitochondrial biogenesis and myofiber regeneration, is limited by rapid plasma clearance and the need for frequent injections. We report the first preclinical evaluation of a transdermal Pyr-Apelin-13 microneedle (MN) patch (HeroPatch) in aged mice. The solid-state “drug-in-resin” design achieved near-complete release efficiency ( $$\approx$$ 100% in vitro ; 83–99% in vivo ), enabling reproducible multi-milligram delivery with minimal residual loss. Daily MN dosing significantly improved muscle fiber cross-sectional area and grip strength relative to controls, with outcomes comparable to daily intraperitoneal injection. Histological analysis revealed a shift toward larger fiber sizes, consistent with enhanced myofiber remodeling, and mitochondrial DNA content increased concordantly. Weekly dosing produced smaller, non-significant trends, reflecting lower cumulative exposure. These findings demonstrate that HeroPatch enables efficient, reproducible, and non-invasive systemic delivery of Apelin-13, providing a scalable platform for peptide-based therapy of sarcopenia and related muscle-wasting disorders.