Applications of chitosan derivatives as adjuvants for nanoparticle‐based vaccines: A comprehensive review

Abstract The development of safe and effective vaccines remains a critical priority in modern medicine. Traditional adjuvants, while effective in enhancing immune responses, often suffer from limitations including local reactogenicity, limited mucosal immunity, and instability of antigens. Chitosan, a natural polysaccharide derived from chitin, and its derivatives have emerged as promising candidates for nanoparticle‐based vaccine delivery due to their biocompatibility, biodegradability, mucoadhesive properties, and intrinsic immunostimulatory activity. Chemical modifications of chitosan, such as trimethylation, quaternization, and thiolation, enhance its solubility, stability, and immune modulatory functions. Chitosan derivative nanoparticles (CDNPs) facilitate efficient antigen encapsulation, protect labile biomolecules, and promote uptake by antigen‐presenting cells. They can trigger both humoral and cellular immune responses, particularly through mucosal administration routes. This review comprehensively discusses the physicochemical properties of chitosan derivatives, mechanisms of immune enhancement, methods for nanoparticle preparation, applications in preclinical and clinical vaccine studies, and challenges for translation to human use. Insights from recent literature suggest that CDNPs hold significant potential to revolutionize vaccine delivery platforms, especially for mucosal vaccines and next‐generation immunotherapeutics.