Investigation of muscone as transdermal penetration enhancer: Enhancing activity and molecular mechanisms

The aim of this present study was to investigate the enhancing activities of animal-derived muscone on the transdermal permeation of drugs with different lipophilicities and shed light on its possible mechanisms of action. The epidermal keratinocytes and dermal fibroblast cell lines were employed to evaluate the cytotoxicity of muscone using MTT assay. A series of model drugs with a wide range of lipophilicity were tested using in vitro permeation studies in which Franz diffusion cells and rat skin were used. The saturation solubilities and SC/vehicle partition coefficients of model drugs were measured to monitor the effect of muscone on drug thermodynamic activities and partition of drug into SC layer, respectively. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and Raman spectroscopy were used to understand the effect of muscone on molecular organization of the stratum corneum (SC). It was found that muscone displayed lower cytotoxicity than the commonly-used and standard penetration enhancer Azone. Meanwhile, muscone could significantly promote the percutaneous absorption of all of five model drugs. The molecular mechanism studies revealed that muscone could enhance the skin permeability predominantly by interacting with the SC lipids, especially the disorder of the lipid bilayer packing. These results suggested that muscone could be a safe and efficient penetration enhancer in the external use.