The objective of this study was to investigate the influence of surfactant charge, surfactant carbon chain length, and surfactant content on the physicochemical characteristics (ie, vesicle size, zeta potential, elasticity, and entrapment efficiency), morphology, stability, and in vitro skin permeability of meloxicam (MX)-loaded liposome. Moreover, the mechanism for the liposome-enhanced skin permeation of MX was determined by Fourier transform infrared spectroscopy and differential scanning calorimetry. The model formulation used in this study was obtained using a response surface method incorporating multivariate spline interpolation (RSM-S). Liposome formulations with varying surfactant charge (anionic, neutral, and cationic), surfactant carbon chain length (C4, C12, and C16), and surfactant content (10%, 20%, and 29%) were prepared. The formulation comprising 29% cationic surfactant with a C16 chain length was found to be the optimal liposome for the transdermal delivery of MX. The skin permeation flux of the optimal formulation was 2.69-fold higher than that of a conventional liposome formulation. Our study revealed that surfactants affected the physicochemical characteristics, stability, and skin permeability of MX-loaded liposomes. These findings provide important fundamental information for the development of liposomes as transdermal drug delivery systems.

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