Emulsome-Based Nanocarrier System for Controlled 4-Phenylbutyric Acid Delivery and Mechanistic Mitigation of Arsenical-Induced Skin Injury via Foam Application

<b>Background</b>: Lewisite, a potent chemical warfare agent, induces rapid and progressive cutaneous damage, necessitating treatment strategies that offer both immediate decontamination and prolonged therapeutic action. This study aimed to develop and evaluate a composite topical formulation comprising 4-phenylbutyric acid (4-PBA)-loaded emulsomes embedded within a foam vehicle to address both aspects of vesicant-induced skin injury intervention. <b>Methods</b>: Emulsomes composed of a stearic acid-cholesterol solid lipid core stabilized by a lecithin shell were prepared via thin film hydration and optimized by varying lipid ratios and drug loading parameters. Formulations were characterized for drug loading, particle size, and zeta potential. Physicochemical compatibility was assessed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses. Stability was evaluated under accelerated refrigerated (25 °C/60% RH) and room temperature (40 °C/75% RH) conditions. The optimized formulation was incorporated into a foam base and evaluated for decontamination efficiency, drug release kinetics, in vitro permeation, and in vivo efficacy. <b>Results</b>: The selected formulation (E2) exhibited high drug loading (17.01 ± 0.00%), monodisperse particle size (PDI = 0.3 ± 0.07), and stable zeta potential (-40 ± 1.24 mV). FTIR and DSC confirmed successful encapsulation with amorphous drug dispersion. The emulsome-foam demonstrated dual functionality: enhanced decontamination (66.84 ± 1.27%) and sustained release (~30% over 24 h), fitting a Korsmeyer-Peppas model. In vitro permeation showed significantly lower 4-PBA delivery from E2 versus free drug, confirming sustained release, while in vivo studies demonstrated therapeutic efficacy. <b>Conclusions</b>: This emulsome-foam system offers a promising platform for topical treatment of vesicant-induced skin injury by enabling both immediate detoxification and prolonged anti-inflammatory drug delivery.