Revolutionizing Drug Delivery: Biodegradable Polymeric Nanoparticlesfor Enhanced Therapeutic Efficacy

Conventional drug delivery systems are often limited by poor bioavailability, premature drug degradation, and lack of targeted release, underscoring the need for innovative carriers that enhance therapeutic efficacy. Biodegradable polymeric nanoparticles (PNPs) have emerged as a promising solution, yet their design–function relationships and translational potential remain fragmented across the literature. This review provides a comprehensive overview of current advances in the synthesis, structural engineering, and biomedical applications of biodegradable PNPs. Biocompatible polymers such as chitosan, poly(lactic-co-glycolic acid) (PLGA), and poly(lactic acid) (PLA) are highlighted for their ability to encapsulate therapeutic agents and enable controlled release at disease-specific sites. Fabrication techniques, including electrospraying, emulsion–solvent evaporation, and nanoprecipitation, are discussed in relation to particle size, drug-loading capacity, and release kinetics. Special emphasis is placed on surface modification strategies such as PEGylation and ligand conjugation that extend circulation time and achieve precise tissue targeting. In addition, preclinical evaluations of in vitro and in vivo performance are summarized, focusing on stability, safety profiles, and therapeutic outcomes. By integrating design principles, mechanistic insights, and translational challenges, this study offers a critical assessment of the state of the art in biodegradable PNPs. We conclude that PNPs hold strong potential for personalized and sustained therapies with reduced side effects. Remaining challenges, such as scalable manufacturing, long-term stability, and immunogenicity, must be addressed, and emerging solutions, including AI-guided design and hybrid polymer systems, provide promising avenues for future research