Design, development, and characterization of stimuli-responsive polymeric carriers for colon-specific drug delivery: A promising approach for capecitabine

Colorectal cancer remains one of the leading causes of cancer-related mortality worldwide, underscoring the urgent need for advanced drug delivery systems that enhance therapeutic efficacy while minimizing systemic toxicity. In this study, pH-responsive hydrogel-based polymeric carriers were developed and characterized for the delivery of capecitabine (CT), a chemotherapeutic drug used to treat colorectal cancer. Hydrogels were synthesized by crosslinking synthetic (cellulose acetate phthalate) and natural (pectin, guar gum) polymers to confer pH-sensitive behavior. A total of eleven formulations (F1–F11) were evaluated for encapsulation efficiency (EE%), swelling behavior, and in vitro drug release under simulated gastrointestinal conditions (pH 1.2 and 7.4). Among these, the optimized formulation F5 demonstrated superior performance, achieving EE% values of 62.00 ± 0.85 % at pH 1.2 and 86.49 ± 0.94 % at pH 7.4, indicating effective gastric protection and enhanced colonic targeting. Swelling studies confirmed pH-dependent expansion, with a swelling index of 76.70 % at pH 7.4 and negligible swelling at pH 1.2. In vitro release studies showed sustained CT release over 24 h, with 62 % release at pH 1.2 and 86 % at pH 7.4. The release kinetics followed the Korsmeyer–Peppas model (R² = 0.996, n = 0.565), suggestive of anomalous (non-Fickian) transport. Physicochemical characterizations confirmed successful drug encapsulation and polymer compatibility via FTIR, while SEM analysis revealed a porous hydrogel architecture. Furthermore, DSC and XRD analyses indicated the amorphous dispersion of CT within the polymeric matrix. Acute oral toxicity studies conducted in mice demonstrated the hydrogel's biocompatibility, with no significant alterations in hematological, biochemical, or histopathological parameters. These findings establish formulation F5 as a promising colon-targeted drug delivery system for capecitabine, capable of enhancing therapeutic outcomes, reducing dosing frequency, and minimizing systemic toxicity. This study supports the potential of pH-responsive hydrogels as effective platforms for colorectal cancer therapy.