• • WRK peptide achieves 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, demonstrating potent antibacterial and antibiofilm efficacy under anaerobic conditions.
• • The AMP-loaded microneedles (MNs) exhibit sufficient mechanical strength to penetrate skin, enabling effective dermal delivery of WRK peptide for localized treatment of subcutaneous P. acnes infections.
• • In a mouse back acne model, AMP MN treatment significantly reduced inflammation and cleared P. acnes infection, with histological analysis showing reduced inflammatory cell infiltration and fibrous tissue hyperplasia compared to the blank MN group (skin thickness 2000–2400 μm).
• • AMP MNs outperformed commercial clindamycin gel in therapeutic efficacy, offering a non-antibiotic strategy that avoids drug resistance development, a critical advantage given the >50% resistance rates of P. acnes to erythromycin and clindamycin in many regions.