Temperature-Responsive Hydrogel for Silver Sulfadiazine Drug Delivery: Optimized Design and In Vitro/In Vivo Evaluation

Abstract

Response surface methodology (RSM) was applied to optimise a temperature-responsive hydrogel formulation synthesised via the direct incorporation of biocellulose, which was extracted from oil palm empty fruit bunches (OPEFB) using the PF127 method. The optimised temperature-responsive hydrogel formulation was found to contain 3.000 w/v% biocellulose percentage and 19.047 w/v% PF127 percentage. The optimised temperature-responsive hydrogel provided excellent LCST near to the human body surface temperature, with high mechanical strength, drug release duration, and inhibition zone diameter against Staphylococcus aureus. Moreover, in vitro cytotoxicity testing against human epidermal keratinocyte (HaCaT) cells was conducted to evaluate the toxicity of the optimised formula. It was found that silver sulfadiazine (SSD)-loaded temperature-responsive hydrogel can be used as a safe replacement for the commercial SSD cream with no toxic effect on HaCaT cells. Last, but not least, in vivo (animal) dermal testing—both dermal sensitization and animal irritation—were conducted to evaluate the safety and biocompatibility of the optimised formula. No sensitization effects were detected on the skin applied with SSD-loaded temperature-responsive hydrogel indicating no irritant response for topical application. Therefore, the temperature-responsive hydrogel produced from OPEFB is ready for the next stage of commercialisation.