Mupirocin-Piperine Microemulsion Hydrogels Accelerate Healing of Infected Wounds through Deep Penetration and Biofilm Disruption.

The emergence of bacteria resistant to multiple first-line antibiotics has created an urgent demand for effective alternatives and a comprehensive approach to the healing of infected wounds. This study developed synergistic microemulsion hydrogels (Mup-Pip-ME-gels) combining piperine's biofilm-disrupting properties with mupirocin's antibacterial activity to combat antibiotic resistance and enhance wound healing. The optimization of the formulation was carried out using a pseudoternary phase diagram and response surface methodology, resulting in a microemulsion with stable physical properties: an average particle size of 57.54 nm and a zeta potential of -15.3 mV. This microemulsion was then incorporated into hydroxypropyl methylcellulose-based hydrogels for further investigation. The results demonstrated that the hydrogels exhibited excellent stability, minimal skin irritation, and significantly enhanced cumulative permeation compared with commercial products (Bactroban). Mup-Pip-ME-gels showed the largest inhibition zones against both and MRSA, measuring 46.0 ± 0.20 and 50.5 ± 0.50 mm, respectively, and achieved a significant biofilm disruption with inhibition rates of 85.0 ± 0.3% and 81.2 ± 0.7%. Pharmacodynamic studies indicated a 2.2-fold increase in the wound healing rate and a significant reduction in bacterial count ( < 0.01) by day 7. Overall, by combining natural compounds and antibiotics, Mup-Pip-ME-gels enhance transdermal permeation and wound healing while addressing antibiotic resistance, offering an effective topical treatment for bacterial infections.