In-situ forming alginate dialdehyde-gelatin hydrogel for sustained silver sulfadiazine delivery: <i>in-vivo</i> evaluation in a preclinical burn wound model

This study aimed to develop and optimize an in situ forming alginate dialdehyde (ADA)-gelatin hydrogel for sustained topical delivery of silver sulfadiazine (SSD) and to evaluate its burn wound healing efficacy in a preclinical rat model. ADA was synthesized and combined with gelatin to form a Schiff-base-cross linked network, enabling rapid gel formation upon mixing in a borax containing medium. A 32 factorial design was used to study the effects of ADA (X1) and gelatin (X2) concentrations on viscosity, gelation time, and SSD release at 10 h, and to identify an optimized formulation using desirability-based optimization. The optimized SSD-loaded hydrogel showed rapid gelation (∼90 s), near neutral pH (∼7.2), and high SSD assay (≈99% of theoretical loading), with shear thinning behavior suitable for topical application. SEM indicated a porous microstructure, and physico-mechanical testing supported appropriate gel strength and moisture management characteristics. In vitro release demonstrated sustained SSD delivery over 10 h, consistent with diffusion/relaxation controlled kinetics. In vivo, the SSD loaded hydrogel achieved ∼99% wound closure by day 14, outperforming the hydrogel base (∼93%) and a marketed SSD cream (∼84%). Overall, the ADA-gelatin in situ hydrogel provided rapid wound conformability, sustained SSD release, and improved burn healing, supporting its potential as an advanced topical therapy for burn wound management.