Effect of pyrrolidone derivatives on lipid membrane and protein conformation as transdermal penetration enhancer.
Effect of pyrrolidone derivatives on lipid membrane and protein conformation has been assessed to obtain fundamental information about a mechanism of transdermal penetration enhancer. Their effects on a release of 6-carboxyfluorescein from liposome were examined. The lipophilic derivatives enhanced a release of dye and the enhancing effect showed a concentration dependency. Especially 1-lauryl-2-pyrrolidone showed the highest effect at the lowest concentration. The pyrrolidone derivatives also increased a hemolysis of rat erythrocytes. The derivatives slightly liberated SH group of keratin but did not change the electrophoresis pattern of keratin. 1-Methyl-2-pyrrolidone increased and retained a hydration of rat skin although 1-hexyl- and 1-lauryl-2-pyrrolidone showed no increase. These results suggest that the high enhancing effect of II, III and IX, as shown in the previous study, may be predominantly due to their interaction with skin lipid and their penetration behavior into the lipid.
Sasaki
H
H
Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Kishikawa
M
M
Nakamura
J
J
Shibasaki
J
J
D000818:Animals; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D005452:Fluoresceins / Q000008:administration & dosage; D005712:Galvanic Skin Response; D006461:Hemolysis / Q000187:drug effects; D007633:Keratins / Q000737:chemistry; D008081:Liposomes; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry*; D015394:Molecular Structure; D011487:Protein Conformation / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014867:Water / Q000032:analysis
D004337:Drug Carriers; D005452:Fluoresceins; D008081:Liposomes; D008563:Membrane Lipids; D011760:Pyrrolidinones; D013438:Sulfhydryl Compounds; D014867:Water; C024098:6-carboxyfluorescein; D007633:Keratins