Development of Terpene-Containing Polymeric Micelles and Evaluation of Their Potential Skin Penetration Pathways for Improving Dermal Delivery of Resveratrol

Background/Objectives: This study aimed to develop a novel polymeric micelle formulation using poloxamer 184 with ethanol and various terpenes to improve the skin penetration of resveratrol. Methods: The terpenes used in this study were monoterpenes, namely, d-limonene, citral, and cineole. Polymeric micelles were prepared by direct dissolution method. The prepared polymeric micelles were composed of 1% terpenes, 25% poloxamer 184, 5% ethanol, and 69% water. Resveratrol was successfully loaded into the polymeric micelles at a concentration of 0.24 mg/mL. The obtained polymeric micelles were characterized for their size, surface charge, and size distribution. The skin penetration pathway of the micelles was investigated using dual fluorescently labeled particles and observed via confocal laser scanning microscopy. Results: The average particle size of the prepared polymeric micelles ranged from 29.02 ± 2.28 to 57.16 ± 8.32 nm, exhibiting a neutral surface charge and an acceptable size distribution. The in vitro skin penetration study revealed that polymeric micelles with ethanol and d-limonene significantly increased the skin penetration of resveratrol compared with the resveratrol ethanolic solution as control. These polymeric micelles penetrated the skin primarily via the intercellular and transcellular pathways, whereas the transfollicular pathway served as a minor route. The particles also penetrated the skin through the intercluster pathway. Conclusions: The polymeric micelles with d-limonene effectively enhanced dermal delivery of resveratrol by facilitating its penetration through the skin via intercellular and transcellular pathway as major penetration pathway.