Dual drug-loaded dissolving microneedle combining photodynamic therapy and isotretinoin for enhanced acne vulgaris treatment.

Acne vulgaris is a multifactorial inflammatory skin disorder driven by excessive sebum secretion, follicular obstruction, and Cutibacterium acnes (C. acnes) proliferation. Conventional topical treatments often suffer from insufficient drug penetration and challenges in co-delivery of drugs with contrasting physicochemical properties. In this study, a dual drug-loaded dissolving microneedle (MN) system was developed for the simultaneous transdermal delivery of the hydrophilic photosensitizer precursor 5-aminolevulinic acid (ALA) and the hydrophobic retinoid isotretinoin (IT). IT was encapsulated in Pluronic F127 micelles via thin-film hydration, and the resulting micelles were incorporated together with ALA into a hyaluronic acid matrix to fabricate dissolving MNs by mold casting. The fabricated MNs exhibited well-defined morphology and sufficient mechanical strength to penetrate the stratum corneum. Dynamic light scattering (DLS) analysis confirmed that the micellar structure was preserved during MN fabrication and dissolution, enabling IT to be released in micellar form with a relatively slower permeation profile, while ALA was rapidly released. In vitro studies demonstrated that ALA-PDT effectively eradicated C. acnes and inhibited lipid synthesis in sebocytes, while IT independently suppressed sebocyte lipogenesis. Notably, the combination of ALA-PDT and IT achieved enhanced inhibition of lipid synthesis compared to either treatment alone. Cytocompatibility assays confirmed the favorable biosafety of the MN system. This dual drug-loaded dissolving MN platform enables efficient co-delivery of hydrophilic and hydrophobic drugs and achieves complementary anti-acne effects through distinct mechanisms, offering a promising strategy for acne treatment.