Synthesis, Characterization, In vitro and In vivo Evaluation of Pullulan-co-MAA Hydrogels Decorated with 5-fluorouracil for Oral-Colonic Delivery

Introduction: Conventional treatment of colorectal cancer causes severe side effects, leading to non-compliance. Hydrogels are polymer-based oral drug delivery carriers that offer numerous advantages. Methods: This study describes the application of the free-radical polymerization approach for the synthesis of colon-targeted, pH-responsive, pullulan-co-MAA hydrogels to deliver 5-fluorouracil. The prepared hydrogels were characterized in vitro and in vivo. Results: In vitro characterizations confirmed successful crosslinking, a decrease in the drug’s crystallinity, a rough morphology, and the stable nature of the drug. Gel content, swelling index, porosity, and drug entrapment efficiency were increased with the increase in the concentration of polymer and monomer. The drug release followed a swelling study pattern; the cumulative drug release was increased with the increase in concentration of polymer (80.4% to 95.6%) and monomer (72.1% to 78.3%), while cross-linker negatively affected the drug release (62.2% to 53.5%) at pH 7.4. The results of the MTT-assay showed that blank hydrogels were cyto-compatible as all the cells displayed more than 95% viability, while drug-loaded hydrogels exhibited dose dose-dependent cytotoxic effect. Oral tolerability results showed that the hydrogel suspension was well-tolerated up to 4000mg/kg of body weight without altering hematology and serum chemistry profile or tissue histology of various organs. Discussion: The results confirmed successful hydrogel formation with effective 5-fluorouracil entrapment, enhanced thermal stability, and controlled drug release influenced by the concentrations of polymer, monomer, and crosslinker. Conclusion: According to findings, the fabricated hydrogels have promising potential to deliver 5- fluorouracil and other hydrophilic moieties into the colon.