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.
Lee
Kyoung-Jin
KJ
Locus Discovery Inc., Blue Bell, PA 19422, USA.
Hwang
Sun-Joo
SJ
Kim
Jung Sun
JS
Kim
Dae-Duk
DD
Shin
Young-Hee
YH
Lee
Chi-Ho
CH
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