Chitosan-Based Drug Delivery Systems for Targeted Chemotherapy in Colorectal Cancer: A Scoping Review

Chitosan (CS) has emerged as a versatile biopolymer for designing drug delivery systems (DDS) in colorectal cancer (CRC) therapy due to its biocompatibility, mucoadhesive properties, and ability to be surface-functionalized. This scoping review systematically analyzed current experimental studies on CS-based DDS for CRC, comparing non-targeted formulations with ligand-modified systems to identify advances in targeting efficiency, drug release behavior, and biological outcomes. Among the twenty-five initially identified studies, divided into two categories, non-targeted CS-based DDSs and ligand-modified CS-DDSs, five fulfilled the inclusion criteria for ligand-functionalized systems. These incorporated targeting moieties, such as folic acid (FA), hyaluronic acid (HA), and galactose (Gal), to achieve receptor-mediated uptake via FRα, CD44, and ASGP receptors, respectively. Ligand modification consistently enhanced cellular uptake, reduced IC₅₀ values, and improved tumor-selective cytotoxicity compared to non-targeted systems. However, in vivo validation remains scarce, with only one study confirming tumor accumulation in xenograft models. Moreover, no clinical trials currently assess CS-based nanocarriers for the treatment of CRC. Overall, CS represents a promising modular platform for targeted nanomedicine, but translational progress requires bridging preclinical success with comprehensive in vivo and clinical evaluation.