A COMPREHENSIVE REVIEW OF CHITOSAN NANOPARTICLES AND DELIVERY SYSTEMS

Chitosan is a naturally derived, cationic polysaccharide obtained by partial deacetylation of chitin and has become an important platform in modern pharmaceutical technology because of its biodegradability, biocompatibility, mucoadhesion and chemically reactive amino and hydroxyl groups. These characteristics permit the construction of nanoparticles, nanogels, microspheres, hydrogels, films, polyelectrolyte complexes and hybrid nanocarriers capable of improving drug solubility, stability, residence time, cellular uptake and controlled release. This review examines the pharmacological and biopharmaceutical properties of chitosan and discusses the major chitosan-based delivery systems, their preparation principles and their suitability for different routes of administration. Particular emphasis is placed on passive, active and stimulus-responsive targeting, including pH-, temperature-, enzyme-, redox- and light-responsive systems. Recent developments in DNA, RNA, siRNA, mRNA and CRISPR-associated delivery demonstrate the potential of chitosan as a non-viral gene-delivery platform, while hybrid systems extend its utility toward theranostics and multimodal therapy. Despite substantial preclinical progress, clinical translation is limited by variability in molecular weight and degree of deacetylation, formulation reproducibility, colloidal stability, sterilization, scale-up, long-term safety and regulatory characterization. Future progress will depend on standardized pharmaceutical-grade chitosan, quality-by-design approaches, mechanistic understanding of biological interfaces and clinically relevant pharmacokinetic and toxicological studies. Overall, chitosan should be viewed not simply as an excipient but as a tunable delivery platform capable of integrating controlled release, targeting and biological functionality.