Enzymatically degalactosylated xyloglucan in situ gels for topical delivery of triamcinolone acetonide.

Thermoresponsive in situ gelling systems are attractive platforms for topical ocular delivery because they can be administered as liquids and rapidly form gels at the ocular surface, thereby increasing residence time and sustaining drug release. This study investigated whether enzymatic degalactosylation of tamarind-seed xyloglucan could be used to develop thermoresponsive hydrogels for the delivery of triamcinolone acetonide (TA). Degalactosylation kinetics, monitored by monosaccharide analysis and oligosaccharide profiling, showed rapid initial galactose removal followed by a plateau near 50%. This structural evolution modified xyloglucan oligosaccharide motifs and induced thermoresponsive gelation after substantial degalactosylation. Among the modified samples, Deg50-XG showed the most suitable thermal transition. At 3.0% (w/v), it gelled at 35°C within about 68 s and formed the strongest elastic network. Contact with simulated tear fluid was found to be a second, independent gelation trigger: at an identical polymer concentration of 1.5% (w/v), the sol-gel transition shifted from 36.4°C in water to 25.7°C, i.e. from above to well below ocular surface temperature, and an elastic network with a storage modulus approximately three orders of magnitude higher was formed at 35°C. In vitro release studies showed that increasing polymer concentration slowed TA release and reduced dissolution efficiency, consistent with denser hydrogel networks. Kinetic analysis indicated that the relative contribution of network relaxation and erosion to drug transport increased with polymer concentration, while release remained consistent with a matrix containing dispersed, poorly soluble drug. These results show that controlled enzymatic tailoring of xyloglucan can be used to tune gelation behavior and drug-release performance in dually thermo- and ion-triggered thermoresponsive in situ gelling systems for sustained topical delivery of TA.