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 (C2-C8) 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, EHMS) 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 corneum lipid liposome bilayer was studied by comparing the enhancement factor for the lipoidal pathway in the hairless mouse skin, EHMS, with that for the stratum corneum lipid liposome, ESCLL, 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 corneum lipid liposomes were determined, and the ESCLL values for these permeants were compared with the EHMS 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoneto
K
K
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City 84112, USA.
Li
S K
SK
Ghanem
A H
AH
Crommelin
D J
DJ
Higuchi
W I
WI
D000818:Animals; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism*; D008353:Mannitol / Q000378:metabolism; D008433:Mathematics; D051379:Mice; D015394:Molecular Structure; D010539:Permeability / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects*; D013395:Sucrose / Q000378:metabolism; D013552:Swine; D013997:Time Factors
D008081:Liposomes; D011760:Pyrrolidinones; D008353:Mannitol; D013395:Sucrose