Harnessing 5-fluorouracil-loaded chitosan nanoparticles for targeted colon cancer therapy

Colon cancer remains a significant global health burden, and although 5-fluorouracil (5-FU) is a cornerstone chemotherapeutic agent, its clinical utility is constrained by systemic toxicity and poor tumor selectivity. This review highlights recent advances in chitosan-based nanoparticles as targeted delivery systems for 5-FU in colon cancer therapy. Chitosan, a biocompatible and biodegradable polymer, offers advantages such as mucoadhesion and pH sensitivity, making it well-suited for colon-specific drug delivery. The review covers formulation strategies, physicochemical characterization, and in vitro/in vivo performance of 5-FU-loaded chitosan nanoparticles. Emphasis is placed on active targeting approaches, including ligand functionalization (e.g., folate and hyaluronic acid) to enhance receptor-mediated uptake in cancer cells. Additionally, the pH-responsive behavior of chitosan systems is discussed as a mechanism for controlled drug release within the acidic tumor microenvironment. Preclinical evidence indicates that chitosan nanoparticles improve the therapeutic index of 5-FU by enhancing tumor accumulation and minimizing off-target toxicity compared to the free drug. Overall, this nanocarrier system represents a promising strategy for safer and more effective colon cancer treatment. Literature was systematically sourced from PubMed, Scopus, Web of Science, and Google Scholar (2000-June 2025).