Synthesis and characterization of 5-aminosalicylic acid-azobenzyl-chitosan conjugates-based prodrugs for the colon targeted delivery in dextran sodium sulfate (DSS)-induced ulcerative colitis.

Site-specific colon drug delivery is crucial in the treatment of colon-localized diseases. In this study, prodrugs of 5-aminosalicylic acid (5-ASA), the drug of choice in ulcerative colitis (UC), were synthesized by conjugating with chitosan having molecular weights (MW) of 30, 80 and 300 kDa to achieve targeted delivery to the colon. FT-IR and UV-Vis analyses confirmed the successful synthesis and varying loading capacities of 5-ASA, with a maximum loading capacity of 11.32 ± 2.0 %. The obtained conjugates (7-9) exhibited gradual drug release characteristics, with up to 30 % of the drug content released after 24 h, in the simulated colonic fluid containing rat gastrointestinal (GI) tract homogenates, demonstrating their colon-specific and slow-release properties. The conjugates were non-toxic to normal human colon epithelial cells at concentrations up to 5-10 μg/mL, suggesting a favorable safety profile. Additionally, conjugate (7) was tested for its efficacy in a mouse model of ulcerative colitis. Necropsy results showed no significant structural changes or lesions in animals treated with conjugate (7). Histopathological analysis revealed mild, multifocal lymphoplasmacytic infiltrates and scattered eosinophils in the lamina propria, indicating a low level of inflammation. Overall, the findings suggest that 5-ASA-azobenzyl-chitosan conjugates hold promise as a potential therapeutic option for ulcerative colitis and other colon localized disorders, with minimal side effects due to reduced systemic exposure.