Nanostructured lipid carrier-mediated delivery of testosterone propionate attenuates lipopolysaccharide-induced muscle wasting and improves functional performance in mice

초록

Age-related muscle wasting or “sarcopenia” presents a significant challenge in super-aged societies, and there is no specific drug approved for its treatment yet. Herein, testosterone propionate-loaded nanostructured lipid carriers (TSP-NLCs) designed to prolong drug release and improve muscle wasting are described. Fabricated with nano-template engineering technique using biocompatible lipids (palmityl alcohol and oleic acid) and a surfactant mixture (Tween 40/Span 40/Brij 58), the optimized TSP-NLCs showed small and uniform particles (126 nm), high drug incorporation efficiency (95.5%), and sustained TSP release (70.3%) for 2 days. Following subcutaneous administration to mice in a lipopolysaccharide (LPS)-induced muscle atrophy model, TSP-NLCs improved anti-atrophic effects by restoring LPS-induced body weight, grip strength, and muscle weight loss. Histopathological analysis of the gastrocnemius muscles revealed that TSP-NLCs increased the muscle cross-sectional area (CSA) and decreased fiber shrinkage in mice. TSP-NLCs also ameliorated the effects of LPS on the expression of atrophy-related proteins, myosin heavy chain (MHC), atrogin-1, and muscle ring-finger protein-1 (MuRF1), thereby slowing down muscle degradation. Our findings indicate the effectiveness of TSP-NLCs as a promising therapeutic against LPS-induced muscle wasting, thus paving the way for future sarcopenia treatments. © 2026 Elsevier B.V.

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