Abstract

Topical anesthetics suffer from low efficacy due to poor skin permeability. This study aims to investigate the potential of cold atmospheric plasma (CAP) pretreatment to improve skin permeation of lidocaine HCl, a local anesthetic, from an optimized liposome formulation (LI-LIPO). CAP pre-treatment duration (1, 3, and 5 min) and different working gas compositions (Ar and Ar + O<inf>2</inf> (20%)) were investigated to determine the ideal parameter. In vitro skin permeation studies revealed that the CAP retarded lidocaine HCl skin permeation from optimized LI-LIPO (Enhancement ratio; ER < 1) yet enhanced the permeation of the drug from the control solution (1% lidocaine HCl in PBS; pH 7.4) (ER > 1). Notably, CAP treatment using Ar + O<inf>2</inf> (20%) for 1 min exhibited the highest ER value from the control solution (ER = 12.92). The results of skin characterization studies including contact angle measurement, DSC, and ATR-FTIR analysis supported by CLSM images indicated CAP induced alteration in skin lipid structure and increased hydrophilicity resulting to improved permeation of the control solution on CAP treated skin ascribed to plasma-induced oxidation and lipid peroxidation. Hence, this study has shown that hydrophilic system is suited for permeation enhancement of lidocaine HCl in combination with CAP pretreatment.