Formulation and Optimization of Curcumin-Loaded Chitosan Nanoparticles: A Systematic Study of Solubility Enhancement and Physicochemical Characterization

Curcumin, a polyphenolic compound derived from turmeric, has significantly therapeutic potential through its anti-inflammatory, antioxidant, and antimicrobial properties. However, its clinical application is severely limited by its poor aqueous solubility and low oral bioavailability. This study systematically evaluated the formulation and optimization of curcumin-loaded chitosan nanoparticles (CRCSNPs) via ionic gelation to overcome the limitations. Using a one-factor-at-a-time approach, critical parameters—including chitosan-to- sodium tripolyphosphate (TPP) mass ratio, pH, and curcumin loading—were methodically evaluated to identify optimal formulation conditions. The results demonstrated that a chitosan-to-TPP ratio of 4:1 at pH 5.0 with 5% w/w curcumin loading produced nanoparticles with a mean size of 211.9±10.6 nm and encapsulation efficiency of 96.88%. Fourier-transform infrared spectroscopy confirmed successful ionic crosslinking and specific interactions between curcumin and chitosan. Additionally, CRCSNPs achieved a 2.0-fold solubility enhancement in acetate buffer pH 4.5 and up to 2.8-fold enhancement in the presence of surfactants in comparison to free curcumin. Nanoparticle tracking analysis revealed a modal size of 162.5 nm, corroborating the dynamic light scattering data and supporting the presence of a well-dispersed nanoparticle population. These findings suggest a rational formulation strategy that supports improvements in curcumin's biopharmaceutical properties, offering further possibilities for pharmaceutical, nutraceutical, and cosmeceutical applications The systematic optimization approach provides a reproducible method for other poorly water-soluble bioactive compounds. Optimizing the chitosan-to-TPP ratio, pH, and curcumin loading allows for the fine-tuning of ionic crosslinking and hydrogen bonding. This results in a stable nanoparticle matrix that directly supports the improved solubility of the drug.