Chitosan-Nanoencapsulated Curcumin for the Treatment of Diabetic Foot Ulcers: A Review

Diabetic foot ulcers (DFUs) are wounds characterized by chronic inflammation and elevated oxidative stress that delay tissue regeneration and render them susceptible to infection, thereby complicating healing. Therefore, treating DFUs effectively is often challenging and requires a combined approach that integrates anti-inflammatory, antioxidant, and antibacterial effects. Curcumin, a widely studied natural compound, has shown promise in wound healing by modulating inflammation, oxidative stress, and infections. However, its bioavailability, absorption, and solubility issues limit its clinical applications. To overcome these limitations, curcumin has been incorporated into nanosystems, such as hydrogels, nanofibers, nanoparticles, vesicles, and micelles, thereby improving its delivery and enabling efficient local administration. Among these nanosystems, those formulated with chitosan are of particular interest due to chitosan's intrinsic wound-healing properties. For that reason, this review comprehensively analyzes the literature on the therapeutic mechanisms of the chitosan-curcumin system for diabetic wound closure and compares them with those of free curcumin. The results show that this system exerts anti-inflammatory, antioxidant, and antimicrobial effects through specific mechanisms, including macrophage polarization, modulation of oxidative stress, and alteration of bacterial cell walls. In addition, significant improvements are observed in key healing processes, including cell migration, fibroblast proliferation, collagen deposition, and re-epithelialization. It should be noted that chitosan not only promotes curcumin release but also contributes to its therapeutic effect through its inherent antimicrobial and hemostatic properties, reinforcing its potential as a comprehensive strategy for the treatment of DFUs.