Enhancing effect of oleic, linoleic, lauric, capric, pelargonic or caprylic acid on tolnaftate penetration into human skin layers

Abstract

Introduction. Intact stratum corneum (SC), the outermost layer of the skin, functions as the main barrier for the penetration to and permeation through the skin for many molecules. In the SC, corneocytes are surrounded by continuous lipid matrix and independently of the molecule passive diffusion by the transcellular (cell→lipid matrix→cell) or intercellular (lipid matrix) route, it has to diffuse through the lipid layers in order to cross the barrier. Therefore, the alteration of SC lipid organization influences the rate and extent of SC resistance to the diffusion process. This reversible alteration might be achieved by adding various chemical penetration enhancers (CPEs) to the drug formulation. The SC lipids, which are arranged into lamellar structures, are composed of ceramides (41%), free fatty acids (9%), cholesterol (27%), cholesteryl esters (10%) and cholesterol sulphate (2%) (Marjukka Suhonen et al., 1999). Lipophilic CPEs interact with lipid hydrocarbon chains, disrupt the order of lipid packing and increase fluidization in the bilayers. In this way, penetration of active compounds into SC and through it is enhanced. Fatty acids belong to the lipophilic CPEs and their penetration enhancing properties are related to the hydrocarbon chain length and the presence of double bonds. Obviously, the vehicle in which the CPE is dissolved also influences the magnitude of enhancement (Foldvari, 2000). Oleic acid is considered to be the most potential CPE among fatty acids due to its cis-monounsaturation and „kink“ formation (Marjukka Suhonen et al., 1999). The aim of our studies was to investigate the enhancing effect of six fatty acids (oleic, linoleic, lauric, capric, pelargonic and caprylic) on tolnaftate penetration into epidermis and dermis of human skin applying in vitro skin penetration experiments. Tolnaftate is an antifungal drug of thiocarbamate class, acting against derm[...].