Abstract
Melasma poses considerable challenges in dermatologic management, particularly due to variable treatment responses and frequent recurrence following conventional interventions. We describe ethosome photothermal therapy (ETHOSOMEPTT, N-Finders Co., Ltd, Korea), an innovative 5-layer nanosystem that integrates transdermal delivery technology with targeted laser energy. The platform incorporates ethosomes, phospholipid vesicles containing ethanol, with plasmonic gold and platinum nanoparticles to provide dual therapeutic mechanisms: enhanced drug penetration and controlled hyperthermia. Upon activation by specific laser wavelengths, this system generates localized heat while facilitating the delivery of active ingredients to deeper tissue layers relative to conventional topical treatments. A clinical example demonstrates its utility: a 42-year-old woman with persistent malar melasma spanning 6 years, who had undergone treatment with hydroquinone, oral tranexamic acid, and neodymium-doped yttrium aluminum garnet laser with insufficient improvement, demonstrated a 68% reduction in Modified Melasma Area and Severity Index after 12 treatment sessions. Treatment was well tolerated, with transient erythema as the primary side effect. The mechanism underlying ethosome photothermal therapy encompasses ethanol-mediated enhancement of stratum corneum permeability, targeted delivery via plasmonic nanoparticles, and controlled thermal effects on tissue structure. This methodology represents a potential advancement in melasma management, particularly for cases demonstrating limited response to conventional therapies.