Synthesis of Functional Pectin‐Based Hydrogels via Thiol‐Maleimide Click Reaction for Enhanced Drug Encapsulation and Release

ABSTRACT This work describes the synthesis and characterization of a novel hydrogel system based on pectin (PT) functionalized with thiol and maleimide groups and cross‐linked by thiol‐maleimide click chemistry. Thiolated PT (PT‐SH) and maleimide‐modified PT (PT‐Ma) hydrogel precursors were synthesized by carbodiimide‐mediated amidation and confirmed by elemental analysis, FTIR, and 1H NMR spectroscopy. The resulting hydrogel exhibited a gelation efficiency of over 80%, swelling degrees ranging from 44% to 80% depending on cross‐linking density, and pH‐sensitive behavior with maximum swelling at pH 8. The hydrogel demonstrated high mechanical stability, with compressive strengths of 20.8–33.2 kPa, increasing with cross‐linking density. As a model drug, ibuprofen was encapsulated with efficiencies of up to 337 mg/g hydrogel and released in a controlled fashion. In vitro release studies showed a slower release in acidic environments, which ranged from 22% to 53% within 6–10 h, and faster release in a slightly alkaline environment, consistent with the swelling profile of the hydrogel. Such properties underline the hydrogel's potential for sustained drug delivery. Pectin hydrogels, upon thiol‐maleimide cross‐linking, are hereby presented to be a strong platform in biomedical applications based on mechanical properties, swelling behavior, and performance in drug delivery.