Nicotinic Acid–Modified Chitosan Nanoparticles for Enhanced Resveratrol Delivery and Anticancer Activity

This study focused on functionalizing chitosan with nicotinic acid, the active form of vitamin B3, to obtain a new derivative (Chi_Nico) with enhanced solubility at physiological pH, improved proton buffering capacity, and in vitro anticancer activity, and to develop resveratrol-loaded nanoparticles (nChi_Nico-RES) for enhanced anticancer performance. Chitosan was modified through EDC-mediated amidation, and successful conjugation was confirmed by FTIR, ¹H NMR, and GPC/SEC analyses. Nicotinic acid grafting increased molecular weight, introduced characteristic amide signals, improved solubility at physiological pH, and enhanced proton buffering capacity. Nanoparticles were prepared by ionotropic gelation and showed sizes of 100-140 nm, PDI values below 0.4, and a positive surface charge of +18 to +20 mV. Blank nanoparticles exhibited minimal cytotoxicity, while resveratrol-loaded formulations demonstrated significant anticancer activity in HeLa cervical cancer cells and HT-29 human colon adenocarcinoma cell line. Notably, nChi_Nico-RES reduced HeLa and HT-29 cell viability more effectively than free resveratrol and nanoparticles based on unmodified chitosan, indicating an additive contribution from nicotinic acid. In contrast, the cytotoxic effect on healthy BJ fibroblasts remained considerably lower, supporting the biocompatibility and selective potential of the system. Overall, nicotinic acid modification improves chitosan's carrier performance and offers a novel strategy by combining two natural bioactive molecules within a single nanoparticle platform.