Skeletal muscle is one of the most abundant tissues in the human body, comprising over 600 muscles that contribute to posture, stability, locomotion, and metabolic regulation. Several muscle disorders represent a significant clinical challenge worldwide. In this context, gene and RNA-based therapeutic strategies, particularly microRNA (miRNA), have emerged as promising approaches for the treatment of muscle disorders. This thesis focuses on the formulation and optimization of functionalized hybrid nanoparticles for active targeting towards skeletal muscle cells in order to provide an effective delivery system for therapeutic miRNAs against genetic disorders affecting skeletal muscles. This work was part of POLIRNA ERC PoC project (contract nr: 101113522) and AFM Telethon SaveAR project.