Effects of HPE-101, a skin penetration enhancer, on human erythrocyte membranes.
The primary aim of this study was to investigate the skin permeation-enhancing mechanism of HPE-101 using erythrocyte ghost cells prepared from human whole blood as a biomembrane model. The extent of hemolysis of erythrocytes induced by HPE-101 was measured using a spectrophotometer at 540nm. The effect of HPE-101 on lipid fluidity was examined by observing the change of intramolecular excimer formation and fluorescence polarization using an intramolecular probe (1,3-bis(pyrene) propane) and a lipid probe (1,6-diphenyl 1,3,5-hexatriene), respectively. Hemolysis of erythrocytes was observed at 0.01mM and completed at 1.0mM of HPE-101. The fluorescence polarization of the ghost membrane decreased with the addition of HPE-101, whereas the intramolecular excimer formation increased. HPE-101 thus enhanced the rotational mobility and the lateral diffusion, thereby decreasing the microviscosity of ghost membranes, implying that HPE-101 increases the lipid fluidity of ghost membranes. Therefore, HPE-101 seems to cause an increase in fluidity of the lipid bilayers in the stratum corneum of the skin, resulting in the reduction of diffusion resistance.
Locus Discovery Inc., Blue Bell, PA 19422, USA.
Kyoung-Jin
KJ
Lee
Sun-Joo
SJ
Hwang
Jung Sun
JS
Kim
Dae-Duk
DD
Kim
Young-Hee
YH
Shin
Chi-Ho
CH
Lee
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000493:pharmacokinetics; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D004058:Diffusion / Q000187:drug effects; D004161:Diphenylhexatriene; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D005454:Fluorescence Polarization / Q000379:methods; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007723:Korea; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008954:Models, Biological; D015335:Molecular Probes; D011721:Pyrenes / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013053:Spectrophotometry / Q000379:methods; D014783:Viscosity / Q000187:drug effects
D000277:Adjuvants, Pharmaceutic; D008051:Lipid Bilayers; D015335:Molecular Probes; D011721:Pyrenes; D011758:Pyrroles; D004161:Diphenylhexatriene; C035116:1,3-di-(1-pyrenyl)propane; C075725:1-(2-(decylthio)ethyl)azacyclopentane-2-one