Antimicrobial Peptide Microneedles with Endogenous ROS-Generating Capacity for the Treatment of Anaerobic Propionibacterium acnes Infection
Anaerobic bacterial infections, prevalent in oxygen-deprived tissues, are recalcitrant to conventional antibiotics due to slow bacterial metabolism and the generation of nutrient-rich niches that foster polymicrobial biofilms. Propionibacterium acnes (P. acnes), a skin commensal, exemplifies this challenge, causing acne vulgaris and implant-associated infections, with rising antibiotic resistance. This study introduces an antimicrobial peptide (AMP), WRK (sequence: WRKFRRFKFRW-NH2), which induces endogenous reactive oxygen species (ROS) production in anaerobic bacteria, exploiting their inherent low ROS tolerance. WRK exhibited potent antibacterial activity, with a minimum inhibitory concentration (MIC) of 4 μg mL−1 against planktonic P. acnes and a minimum biofilm eradication concentration (MBEC) of 64 μg mL−1. To enable dermal delivery, WRK was encapsulated in layered dissolving microneedles (MNs), which demonstrated adequate mechanical strength for skin penetration. In a mouse back acne model, AMP MNs significantly reduced P. acnes infection and inflammation, outperforming commercial clindamycin gel. Histological analysis confirmed reduced inflammatory cell infiltration and tissue hyperplasia in the AMP MN group. This strategy offers a promising approach for treating anaerobic infections without promoting drug resistance, addressing a critical unmet need in clinical dermatology and implant surgery.