Laponite®-Based Smart Hydrogels for Sustained Topical Delivery of Silver Sulfadiazine: A Strategy for the Treatment of Contaminated or Biofilm-Forming Wounds

<b>Background/Objectives</b>: Silver sulfadiazine (AgSD) is widely used in the topical treatment of burns and infected wounds, but its conventional formulations present drawbacks such as poor water solubility, the need for multiple daily applications, and patient discomfort. To overcome these limitations, this study aimed to develop and evaluate Laponite^® (LAP)-based hydrogels loaded with AgSD for controlled release and enhanced antimicrobial and antibiofilm efficacy, offering a promising alternative for the treatment of contaminated or biofilm-forming wounds. <b>Methods</b>: Laponite^®-based hydrogels containing 1% and 1.2% AgSD (LAP@AgSD) were prepared using a one-pot method. The formulations were characterized rheologically, thermally, and structurally. In vitro drug release was assessed using Franz diffusion cells, and mathematical modeling was applied to determine release kinetics. Antibacterial and antibiofilm activities were evaluated against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i> using standardized microbiological methods. <b>Results</b>: LAP@AgSD hydrogels exhibited pseudoplastic behavior, high structural integrity, and enhanced thermal stability. In vitro release assays revealed a sustained release profile, best fitted by the Weibull model, indicating diffusion-controlled mechanisms. Antibacterial assays demonstrated concentration-dependent activity, with LAP@AgSD 1.2% showing superior efficacy over LAP@AgSD 1% and comparable performance to the commercial silver sulfadiazine cream (CC-AgSD). Biofilm inhibition was significant for all formulations, with CC-AgSD 1% exhibiting the highest immediate activity, while LAP@AgSD 1.2% provided sustained antibiofilm potential. <b>Conclusions</b>: LAP-based hydrogels are promising smart delivery systems for AgSD, combining mechanical robustness, controlled drug release, and effective antibacterial and antibiofilm activities. These findings support their potential use in topical therapies for infected and chronic wounds, particularly where biofilm formation is a challenge.