Microneedle-mediated delivery of hydroxypropyl-β-cyclodextrin-encapsulated Angelica sinensis (Danggui) essential oil for acne treatment: efficacy and mechanisms

Acne is a multifactorial dermatological condition driven by Propionibacterium acnes ( P. acnes ) infection, inflammation, and sebum dysregulation. While essential oils, such as Angelica sinensis (Danggui) essential oil (AEO), exhibit antimicrobial and anti-inflammatory properties, their clinical application is hindered by poor solubility, stability, and skin penetration. To address these limitations, we developed hydroxypropyl- β -cyclodextrin (HPCD)-complexed AEO-loaded microneedles (AEO@HPCD MNs) using hyaluronic acid for enhanced transdermal delivery. The optimized AEO@HPCD MNs demonstrated superior mechanical strength, rapid dissolution, and efficient cargo release. In vitro studies confirmed potent antibacterial activity against P. acnes , while in vivo experiments revealed significant reductions in acne lesion size and IL-1 β levels. RNA sequencing of treated acne lesions identified key downregulated genes ( Fpr1 , Rarres2 , Cxcl5 , Gbp3 , Hck , Gbp7 , Librb4a , Psmb8 ) and enriched pathways, including innate immunity and inflammatory responses. Notably, AEO@HPCD MNs suppressed 5 α -reductase and fatty acid synthase (FAS) expression, demonstrating—for the first time—AEO’s ability to normalize sebum production. Mechanistically, AEO@HPCD MNs exert multifaceted therapeutic effects: (1) direct antibacterial activity against P. acnes , (2) suppression of inflammatory and immune-related pathways through modulation of Toll-like receptor, NOD-like receptor, and cytokine-cytokine receptor signaling pathways, (3) regulation of sebum production via lipid-metabolic gene expression modulation, and (4) enhanced delivery efficiency and microenvironment modification through the physical action of microneedles, collectively contributing to synergistic acne therapy. This study develops a microneedle delivery platform that addresses both essential oil instability and inclusion complex delivery challenges while targeting multiple acne pathogenic factors. The AEO@HPCD MNs provide a safe, minimally invasive, multifunctional therapeutic strategy for acne treatment.