A MECHANISTIC STUDY OF THE EFFECTS OF THE 1-ALKYL-2-PYRROLIDONES ON BILAYER PERMEABILITY OF STRATUM-CORNEUM LIPID LIPOSOMES - A COMPARISON WITH HAIRLESS MOUSE SKIN STUDIES

The influence of a series of 1-alkyl-2-pyrrolidones (C-2-C-8) on the transport behavior of lipophilic and polar/ionic permeants across hairless mouse skin was recently investigated by employing a physical model approach that treats the stratum corneum barrier as a diffusional system of parallel lipoidal and pore pathways. In this previous study, the transport enhancement effects (enhancement factor, E(HMS)) on the lipoidal pathway of the stratum corneum were found to be essentially the same for all steroidal probe permeants investigated at Various concentrations of these 1-alkyl-2-pyrrolidones. In the present research, the relationship between solute transport enhancement in the lipoidal pathway of hairless mouse skin and the transport enhancement in the stratum comeum lipid liposome bilayer was studied by comparing the enhancement factor for the lipoidal pathway in the hairless mouse skin, E(HMS), with that for the stratum corneum lipid liposome, E(SCLL), at equal solution concentrations of the 1-alkyl-2-pyrrolidones. The release rates of D-mannitol, D-glucose, 3-O-methyl-D-glucose, sucrose, and raffinose from stratum comeum lipid liposomes were determined, and the E(SCLL) values for these permeants were compared with the E(HMS) values obtained with hairless mouse skin using the steroidal permeants. An important finding in this study was a semiquantitative correlation between the enhancement effects induced by the 1-alkyl-2-pyrrolidones, except 1-ethyl-2-pyrrolidone, with the liposome bilayer using sugar molecules as permeants and those found with the lipoidal pathway in hairless mouse skin using steroid molecules as permeants. The enhancement effects on the barrier properties of the liposome bilayer were found to be reversible at the levels of the 1-alkyl-2-pyrrolidones used in the present study. The transport mechanism of the sugar molecules in the liposome bilayer was also investigated, and analyses involving hindered diffusion calculations and a permeability vs partition relationship suggest that partitioning followed by diffusion in the liposome bilayer is the likely major mechanism in the transport of the sugar molecules out of stratum corneum lipid liposomes; this finding is consistent with the semiquantitative correlation found between E(HMS) and E(SCLL).