K. Yoneto et al., FLUORESCENT-PROBE STUDIES OF THE INTERACTIONS OF 1-ALKYL-2-PYRROLIDONES WITH STRATUM-CORNEUM LIPID LIPOSOMES, Journal of pharmaceutical sciences, 85(5), 1996, pp. 511-517
Previously, the effects of a series of 1-alkyl-2-pyrrolidones (APs; C2
-C8) on the lipoidal pathway of hairless mouse skin (HMS) were studied
with a parallel pathway skin model. At their isoenhancement concentra
tions, these 1-alkyl-2-pyrrolidones induce the same transport enhancem
ent (isoenhancement factor, E(HMS)) on the lipoidal pathway of the str
atum corneum for the probe permeants studied. In the present study, th
e fluidizing effects of APs upon the stratum corneum lipid liposome (S
CLL) bilayer were investigated under these isoenhancement conditions u
sing steady-state anisotropy and fluorescence lifetime studies with fl
uorescent probes 2-, 6-, and 9-(9-anthroyloxy)stearic acids, 16-(9-ant
hroyloxy)palmitic acid, and 1,6-diphenyl-1,3,5-hexatriene to examine a
possible correlation between the fluidizing properties of APs and the
ir enhancement effects on transdermal drug transport. Time-resolved fl
uorescence decay studies were also conducted to further investigate th
e fluidizing properties of APs and add support to the steady-state flu
orescence results. Under an isoenhancement condition of E(HMS) = 10, t
hese APs fluidized the alkyl chains of the lipids at intermediate dept
hs (C6-C9) in the SCLL bilayer (a 40-50% decrease in the rotational co
rrelation times) but did not significantly change the fluidity in the
deep hydrophobic region of the bilayer. Three rotational correlation t
imes were deduced from the global simultaneous analysis in time-resolv
ed fluorescence decay measurements. The slowest of these (greater than
1000 ns) was attributed to the global motion of SCLLs and is probably
related to the static component of steady-state anisotropy. The other
two rotational correlation times (on the order of nanoseconds) were i
n the range expected for the local motion of the fluorophores and may
correspond to their vibrational and rotational motions. When the conce
ntrations of APs were increased (increasing the E(HMS) value), the sta
tic component (a) decreased. This suggests that APs might induce a gen
eral fluidizing effect upon the lipid bilayer (i.e., a decrease in the
order of the lipid bilayer). The decrease in the longer rotational co
rrelation time (on the order of nanoseconds) with increasing E(HMS) va
lue, on the other hand, indicates a possible increase in the ''cavity
volume'' for the hindered motions of the fluorophores (i.e., an increa
se in the free volume at intermediate depths in the bilayer).