Leciplex Nanocarriers: An Optimized Platform for Thymol Delivery in Acne Management

Background/Objectives: Antibiotics are commonly used for acne treatment. However, increasing bacterial resistance has prompted interest in natural antimicrobial agents, such as thymol (THY), as alternative therapies. This study investigated the effectiveness of Leciplex cationic nanovesicles encapsulating thymol (LPX-THY) as a promising topical acne management strategy. Methods: Leciplex nanovesicles were assembled using soy phosphatidylcholine (SPC) and cationic surfactants and characterized in terms of particle size, zeta potential, entrapment efficiency, morphology, in vitro release, and ex vivo skin permeation. The optimized formulation was subsequently incorporated into Carbopol/HPMC gel base and evaluated in terms of viscosity, in vitro release, ex vivo skin permeation, in vitro antimicrobial study, and in vivo assessment in a rat model. Results: Optimal THY-LPX nanovesicles made of SPC and Dimethyldidodecylammonium bromide DDAB in a 1:1 molar ratio showed circular outline with particle size, zeta potential, and entrapment efficiency of 187.7 ± 1.78 nm, 36.97 ±0.21 mV, and 60.5 ± 2.3%, respectively. THY-LPX gel demonstrated minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) at a concentration of 156.25 µg·mL^-1 against Staphylococcus aureus, a clear absence of biofilm coating under SEM, and substantial red fluorescence, indicating reduction in viable bacteria under a confocal laser microscope. In vivo study showed enhanced anti-inflammatory effect evidenced by substantial ear skin thickness reduction; 72.7% for THY-LPX gel-treated rats compared to 41.7% and 20% for THY gel and blank LPX gel-treated groups, respectively. Histopathological investigation further confirmed reduced inflammatory response in rats treated with optimized THY-LPX gel. Conclusions: The developed THY-LPX gel serves as a potential topical delivery platform of THY for acne therapy.