Specific muscle targeted delivery of miR-130a loaded lipid nanoparticles: a novel approach to inhibit lipid accumulation in skeletal muscle and obesity.

BACKGROUND: Skeletal muscle lipid deposition is a key manifestation of obesity, often accompanied by decreased exercise capacity and muscle atrophy. Skeletal muscle as the largest organ in the body, makes it challenges for designing targeted drug delivery systems. Lipid nanoparticles (LNPs) are widely used as a safe and efficient delivery carrier, there is limited research on LNPs that specifically target skeletal muscle. RESULTS: A LNP designed with five specific receptor complements on its surface, which specifically targets skeletal muscle in vivo in mice, without off-target effects on other tissues and organs. MiR-130a, a regulator of PPARG, which is a key factor in skeletal muscle lipid deposition, was encapsulated with LNP (LNP@miR-130a). In high-fat diet (HFD) mice, LNP@miR-130a effectively reduced skeletal muscle lipid deposition, increased exercise activity and enhanced muscle mass. Interestingly, the myokines in skeletal muscle have also changed which may leading to reduce the adipose tissue weight and liver lipid deposition in HFD mice. CONCLUSIONS: These results indicated LNP@miR-130a is a promising inhibitor of skeletal muscle lipid deposition and may help alleviate obesity. This study provides new insights for obesity treatment and lays foundation for the development of targeted skeletal muscle therapeutics.