Augmented silver sulfadiazine nanostructured lipid carriers impregnated collagen sponge for promoting burn wound healing.

Silver sulfadiazine (SSD) is a widely used antibacterial agent for burn wound treatment owing to its capability in re-epithelialization and wound healing. However, due to its low solubility, the need for an effective drug delivery system is mandatory. This study aimed to optimize SSD nanostructured lipid-based carriers (NLCs), incorporated in a collagen sponge form as an innovative topical dosage form for effective burn wound treatment. SSD-NLCs were prepared by applying Box-Behnken design and characterized in terms of particle size, zeta potential, and entrapment efficiency (EE). The optimized SSD-NLCs formula was selected and incorporated into a cross-linked collagen sponge and lyophilized for 24 h. The SSD-NLCs sponge morphological structure, porosity, swelling ratio, in vitro drug release profile and antibacterial activity were assessed. Furthermore, investigating the competitive inhibitory efficiency of SSD against para-aminobenzoic acid (PABA), the native ligand for the dihydropteroate synthetase enzyme based on the calculated binding free energy using the CB-Dock docking server was evaluated. Additionally, the wound healing activity and histopathological studies were evaluated on a second-degree burn wounds in a rat model. The optimized SSD-NLCs were spherical, possessing size of 115.69 ± 3.25 nm, EE% of 89.69 ± 1.36 % and a porosity of 71.22 %. Furthermore, the SSD-NLCs sponge showed an enhanced swelling ratio and improved antimicrobial activity compared to SSD. Finally, in vivo studies in rats showed that SSD-NLCs sponge are effective wound healing formulation owing to their ability to improve the quality of tissue regeneration without scars formation. Results showed that SSD-NLCs sponge can enhance the SSD efficacy in treatment of burn wounds. Further toxicological studies are still needed before clinical application.