Aim <p>This study aimed to enhance the therapeutic efficacy of the antifungal agent Luliconazole (LLCZ) by encapsulating it into PEGylated PLGA polymeric micelles for potential application in seborrheic dermatitis.</p> Methods <p>LLCZ-loaded polymeric micelles were prepared using the thin-film hydration method and optimized through a user-defined statistical design based on particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading. The optimized formula was further evaluated in vitro using release, skin permeation, and deposition studies in porcine skin, along with morphological and thermal characterization. Its therapeutic performance was examined in vivo using a DNCB-induced skin seborrheic dermatitis model in mice.&#xa0;</p> Results <p>The optimized micelles achieved an encapsulation efficiency of 71.7% and a particle size of approximately 102 nm, demonstrating significantly enhanced skin deposition in deeper skin layers compared to the marketed LLCZ, which is expected to improve therapeutic efficiency by overcoming the limited penetration of conventional formulations and potentially reducing the need for frequent application, thereby improving patient compliance and minimizing local side effects.</p> Conclusion <p>These findings highlight m-PEG2100/PLGA2100 micelles as a promising delivery system for improving LLCZ skin delivery.</p>