Sustained-Release Microneedles for Local Delivery of Antibacterial Peptide in Acne Therapy

Acne is a prevalent chronic inflammatory skin disorder with a high recurrence rate, in which Propionibacterium acnes (P. acnes) plays a key pathogenic role by colonizing subepidermal pilosebaceous units. The stratum corneum limits drug penetration, rendering conventional topical therapies ineffective. Herein, we report a detachable sustained-release microneedle system named Bacitracin@Hyaluronic Acid–Zein Microneedle (Bac@HA-ZMN) for localized antibacterial delivery in acne therapy. This microneedle patch consists of a dissolvable HA base and zein-based indwelling microneedle tips loaded with bacitracin (Bac) against P. acnes. Mechanical testing showed an average fracture force of 1.6 N per needle tip (n = 100), sufficient for skin insertion. The needle tips enabled Bac delivery to a depth of approximately 500 μm. In vitro transdermal studies demonstrated a cumulative release of 76.1% within 96 h, significantly higher than that of the control group (14.2%). In a murine acne model, the Bac@HA-ZMN treatment group showed a significantly smaller lesion area than the control group, and the immunohistochemical positive expression areas of the inflammatory factors IL-8, MMP-2, and TNF-α were reduced to 0.79%, 4.12%, and 2.14%, respectively, which was caused by the inhibitory effect of Bac on P. acnes. These results demonstrated Bac@HA-ZMN as a promising localized, sustained antibacterial delivery platform for acne treatment.