Modified 3-Hydroxylbutanoyl Glycan/Gelatin Hydrogels for pH-Responsive Drug Delivery with Enhanced Mechanical Strength and Antioxidant Properties

Rhizobial exopolysaccharide is an eco-friendly and non-toxic biopolymeric materials widely used in various industrial fields such as pharmaceutical, food and cosmetics based on its structural, rheological and physiochemical properties. Rhizobial EPS as a hydrogel biomaterial was used for a pH-responsive drug delivery system combing with gelatins. Pure gelatin (GA) hydrogels have limited practical applications due to their poor mechanical strength and poor thermal stability. We developed GA hydrogels using oxidized 3-hydroxylbutanoyl glycan (OHbG) as a polymer cross-linking agent to overcome these limitations. OHbG was synthesized from sodium periodate oxidation of 3-Hydroxylbutanoyl glycan directly isolated from <i>Rhizobium leguminosarum</i> bv. <i>viciae</i> VF39. OHbG/GA hydrogels exhibited 21-fold higher compressive stress and 4.7-fold higher storage modulus (G') than GA at the same strain. This result suggested that OHbG provided mechanical improvement. In addition, OHbG/GA hydrogels showed effective pH-controlled drug release for 5-fluorouracil and self-antioxidant capacity by uronic acids of OHbG. In vitro, cell viability tests using HEK-293 cells also showed that the OHbG/GA hydrogels were non-toxic. This suggests that rhizobial oxidized 3-hydroxylbutanoyl glycan-based GA hydrogels can be used as a potentially new biomaterial for drug delivery based on antioxidant capacity and pH-responsive drug delivery.