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
K. Yoneto et al., 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, Journal of pharmaceutical sciences, 84(7), 1995, pp. 853-861
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).