Bioinspired Membranes with Silver Sulfadiazine and Piperine for Enhanced Cutaneous Permeability

Developing bioinspired membranes for effective wound healing, particularly for burn injuries, significantly advances biomedical materials. In the present study, we focused on the design and optimization of membranes based on chitosan (CT) and Pluronic F127, incorporating silver sulfadiazine (SSD) for antimicrobial activity and piperine (PIP) as a permeation enhancer. Using a design of experiments with desirability, the optimal membrane composition was determined to be 20 mg/mL CT, 10 mg mL^-1 F127, 0.050 mg mL^-1 SSD, and 0.050 mg mL^-1 PIP, which exhibited excellent homogeneity, mechanical stability, and controlled drug release properties. The membranes were characterized using FTIR, DSC, TGA, AFM, and contact angle measurements, revealing high thermal stability, moderate hydrophilicity, and pH-responsive dissolution behavior. The membranes demonstrated significant water absorption and swelling degree (SD > 500%), creating a moist environment conducive to tissue regeneration. Ex vivo porcine skin permeation studies showed that incorporating PIP more than doubled SSD deposition in both the epidermis (9.82 → 21.75 μg g^-1) and dermis (2.24 → 4.99 μg g^-1). In vitro microbiological assays against Escherichia coli and Staphylococcus aureus (ATCC and clinical strains) revealed that SSD-containing membranes significantly reduced bacterial viability, with the complete membrane (SSD + PIP) showing the strongest inhibition. For E. coli clinical strains, the addition of PIP enhanced the bactericidal effect of SSD (76% vs 33% reduction), consistent with its reported role as an efflux pump inhibitor. Overall, these multifunctional membranes combine sustained SSD release, improved and reproducible skin permeation, and enhanced antimicrobial efficacy in the evaluated strains, offering a promising platform for advanced wound dressings in burn care and other skin injuries.