Chitosan-Curcumin Bioactive Platforms: Mechanistic Synergy, Antimicrobial Performance, and Design Principles for...

Chronic and infected wounds remain difficult to treat due to persistent microbial burden, biofilm formation, and dysregulated inflammation. As a multifunctional polyphenol, curcumin exhibits broad-spectrum antimicrobial, anti-inflammatory, and antioxidant activities. Nevertheless, the clinical application of curcumin is constrained by its limited solubility in water, inherent instability, and insufficient bioavailability. Chitosan, a cationic polysaccharide, provides complementary advantages including intrinsic antimicrobial activity, mucoadhesion, and the capacity to form versatile delivery platforms such as nanoparticles, hydrogels, and films. This review reframes chitosan-curcumin systems as dual-function bioactive platforms in which both the carrier and payload actively contribute to therapeutic outcomes. Mechanistically, chitosan disrupts microbial membranes, enhances bioadhesion, and supports tissue regeneration, while curcumin modulates intracellular targets including reactive oxygen species, quorum sensing, and inflammatory signaling pathways. Their integration enables multimodal antimicrobial activity, improved biofilm disruption, and coordinated regulation of the wound-healing cascade. This review critically examines the structure-function relationships governing release kinetics, stability, and cytocompatibility, with particular emphasis on chitosan molecular weight, degree of deacetylation, crosslinking strategies, and curcumin loading. Solubility-enhancement strategies for curcumin, including surfactants, nanoparticles, solid dispersions, and chemical derivatives, are evaluated in the context of antimicrobial efficacy and cytotoxicity. Finally, the review highlights translational challenges and future directions, such as antibiotic synergy, antifungal applications, formulation complexity, and the emerging role of artificial intelligence in predictive material design. Collectively, these insights establish design principles for next-generation multifunctional biomaterials that integrate antimicrobial activity with immune modulation and tissue repair.