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 t ransport behavior of lipophilic and polar/ionic permeants across hairl ess mouse skin was recently investigated by employing a physical model approach that treats the stratum corneum barrier as a diffusional sys tem of parallel lipoidal and pore pathways. In this previous study, th e transport enhancement effects (enhancement factor, E(HMS)) on the li poidal pathway of the stratum corneum were found to be essentially the same for all steroidal probe permeants investigated at Various concen trations of these 1-alkyl-2-pyrrolidones. In the present research, the relationship between solute transport enhancement in the lipoidal pat hway of hairless mouse skin and the transport enhancement in the strat um comeum lipid liposome bilayer was studied by comparing the enhancem ent 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 rat es of D-mannitol, D-glucose, 3-O-methyl-D-glucose, sucrose, and raffin ose from stratum comeum lipid liposomes were determined, and the E(SCL L) values for these permeants were compared with the E(HMS) values obt ained with hairless mouse skin using the steroidal permeants. An impor tant 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 mo use skin using steroid molecules as permeants. The enhancement effects on the barrier properties of the liposome bilayer were found to be re versible at the levels of the 1-alkyl-2-pyrrolidones used in the prese nt study. The transport mechanism of the sugar molecules in the liposo me bilayer was also investigated, and analyses involving hindered diff usion calculations and a permeability vs partition relationship sugges t that partitioning followed by diffusion in the liposome bilayer is t he likely major mechanism in the transport of the sugar molecules out of stratum corneum lipid liposomes; this finding is consistent with th e semiquantitative correlation found between E(HMS) and E(SCLL).