Preparation of Photoclick‐Crosslinked Modular Gelrite Hydrogel: Tuning Physico‐Chemical Characteristics, Cytocompatibility, In Vitro Cefixime Trihydrate Release, and Antimicrobial Properties

The fabrication of a modular Gelrite-based covalently crosslinked hydrogelator (Gelrite-MA) by photo-initiated click chemistry to facilitate cefixime trihydrate administration is reported for the first time. Modular Gelrite is prepared via base (DIPEA)-catalyzed esterification reaction between Gelrite and maleic anhydride. Under the UV light, the modular Gelrite containing carbon-carbon double bonds undergoes a photocrosslinking reaction with 2, 2'-(Ethylenedioxy)diethanethiol and forms the hydrogelator. Comprehensive characterization of the modular Gelrite-based compound is done using various methods. The significant differences in the hydrogelator's swelling ratio at pH values of 1.2 and 6.8 demonstrate its pH-responsive behavior. The rheological analysis shows that the yield stress value of Gelrite-MA hydrogel is higher at pH 1.2 (2542 Pa) than at pH 6.8 (258 Pa). The Gelrite-MA hydrogel is cytocompatible, showing 128.8 ± 5.9% cell viability against L929 cell lines after 3 days. The Gelrite-MA hydrogel formulation demonstrates sustained release matrix characteristics, releasing 79.4±3.1% of total cefixime over 30 h. The 5 mg hydrogel-cefixime formulation effectively suppresses the inhibition of Escherichia coli and Staphylococcus aureus, with ZOI of 55.3 ± 1.5 mm and 42.0 ± 2.0 mm, respectively. The lower minimum inhibitory concentration value suggests that the hydrogel formulation is more potent against E. coli (MIC = 39 µg/mL) bacteria than S. aureus (MIC = 5 mg/mL). Therefore, the prepared cytocompatible and pH-responsive Gelrite-MA hydrogel has the potential to serve as a sustained drug delivery matrix for administering cefixime trihydrate orally.