Microencapsulation of Alcohol Solvents and High-Content Actives for Efficient Transdermal Delivery

Transdermal delivery offers a patient-friendly route that bypasses hepatic first-pass metabolism, yet the low permeability of the stratum corneum and the poor loading of hydrophobic actives remain major obstacles. Alcohol solvents are effective permeation enhancers and solubilizers, but their high volatility and skin irritation limit direct application. Here, we present a microencapsulation strategy that confines alcohol solvents together with high-content actives within uniform core–shell microcapsules, enabling stable storage and controlled transdermal release. Using a microfluidic emulsification platform, monodisperse droplets were generated and subsequently solidified into robust polymeric shells, precisely tuning capsule size and payload. The encapsulation suppressed premature solvent evaporation while preserving the actives at high loading, and the confined alcohol acted as an in-situ enhancer that transiently increased skin permeability upon application. In vitro release and skin-permeation studies demonstrated that the microcapsules markedly enhanced the transdermal flux of the encapsulated actives compared with free formulations, while reducing irritation associated with bulk alcohol. These results establish a versatile, scalable microencapsulation platform that reconciles high active loading, solvent stability, and efficient skin penetration, offering promising applications in transdermal drug delivery, cosmetics, and functional skincare products.