Rapidly dissolving and detachable microneedles loaded with antimicrobial peptides for acne vulgaris treatment

Acne vulgaris is predominantly caused by Propionibacterium acnes (P. acnes) infection and has a serious impact on the physical and mental health of patients. Conventional treatments like topical and oral drug administrations have their limitations and adverse effects. Microneedles (MNs) are a painless and precise drug delivery system, providing an opportunity to enhance the efficacy of acne treatment. In this work, we construct a rapidly dissolving and detachable hyaluronic acid (HA)-polyvinyl alcohol (PVA) MN loaded with an antimicrobial peptide, ε-poly-L-lysine (EPL). This EPL@MN patch has a compact structure and sufficient mechanical strength to penetrate the skin's stratum corneum. Moreover, the HA tips and PVA substrate of EPL@MN present distinct degradation behaviors. The HA tips exhibit full dissolution within 90 s, ensuring the precise and rapid release of preloaded EPL. The PVA substrate is detachable after the tips release the drug. This EPL@MN patch exhibits excellent antibacterial activity against P. acnes with over 99% killing rate, while exerting minimal impact on the cell viability and proliferation of L929 mouse fibroblasts. In vivo mice acne model studies demonstrate that the EPL@MN patch can effectively inhibit P. acnes and significantly reduce skin swelling by alleviating the levels of inflammatory mediators (TNF-α and CCR-7). Taken together, this rapidly dissolving and detachable microneedle holds promise as a targeted drug delivery system for enhancing acne therapy.