Structural, Swelling, and In Vitro Digestion Behavior of DEGDA-Crosslinked Semi-IPN Dextran/Inulin Hydrogels

Abstract

In this study, semi-interpenetrating polymer network (semi-IPN) hydrogels based on methacrylated dextran and native inulin were designed as biodegradable carriers for the colon-specific delivery of uracil as a model antitumor compound. The hydrogels were synthesized via free-radical polymerization, using diethylene glycol diacrylate (DEGDA) as a crosslinking agent at varying concentrations (5, 7.5, and 10 wt%), and their structural, thermal, and biological properties were systematically evaluated. Fourier transform infrared spectroscopy (FTIR) confirmed successful crosslinking and physical incorporation of uracil through hydrogen bonding. Concurrently, differential scanning calorimetry (DSC) revealed an increase in glass transition temperature (Tg) with increasing crosslinking density (149, 153, and 156 °C, respectively). Swelling studies demonstrated relaxation-controlled, first-order swelling kinetics under physiological conditions (pH 7.4, 37 °C) and high gel fraction values (84.75, 91.34, and 94.90%, respectively), indicating stable network formation. SEM analysis revealed that the hydrogel morphology strongly depended on crosslinking density and drug incorporation, with increasing crosslinker content leading to a more compact and wrinkled structure. Uracil loading further modified the microstructure, promoting the formation of discrete crystalline domains within the semi-IPN hydrogels, indicative of physical drug entrapment. All formulations exhibited high encapsulation efficiencies (>86%), which increased with increasing crosslinker content, consistent with the observed gel fraction values. Simulated in vitro gastrointestinal digestion showed negligible drug release under gastric conditions and controlled release in the intestinal phase, primarily governed by crosslinking density. Antimicrobial assessment against Escherichia coli and Staphylococcus epidermidis, used as an initial or indirect indicator of cytotoxic potential, revealed no inhibitory activity, suggesting low biological reactivity at the screening level. Overall, the results indicate that DEGDA-crosslinked dextran/inulin semi-interpenetrating (semi-IPN) hydrogels represent promising carriers for colon-targeted antitumor drug delivery.