Percutaneous penetration of fluorescein isothiocyanate-dextrans and the mechanism for enhancement effect of enhancers on the intercellular penetration.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Percutaneous penetration of fluorescein isothiocyanate-dextrans and the mechanism for enhancement effect of enhancers on the intercellular penetration.

Biol Pharm Bull. 1995 Nov;18(11):1566-71. Unique Identifier : AIDSLINE MED/96161468
Ogiso T; Paku T; Iwaki M; Tanino T; Faculty of Pharmaceutical Sciences, Kinki University, Osaka,; Japan.

Abstract: To identify the mechanism involved in the enhancement effect of enhancers on the intercellular penetration of large polar molecules, the skin penetration of fluorescein isothiocyanate (FITC)-dextrans (average molecular weight; 4400, 9400, and 69000 Da) and the lipid removal from the intercellular spaces by enhancers were studied using hairless rat skin. Pretreatment of hairless rat skin with enhancers such as n-octanol (20%), laurocapram (2%), isopropylmyristate (IPM, 20%), oleic acid (5%) and cineol (2%), which are water-immiscible, significantly enhanced the flux of FITC-dextrans, while pretreatment with water-miscible enhancers, i.e. dimethyl sulfoxide (DMSO, 5%) and N-methyl-2-pyrrolidone (NMP) did not increase the flux compared with the control. The penetration of FITC-dextrans was approximately size dependent. n-Octanol, laurocapram, IPM and oleic acid dramatically removed ceramides which are the intercellular lipids, whereas NMP and DMSO partly extracted the sphingolipids. A linear relationship was observed between the flux and removal of ceramides (p < 0.01), indicating that the removal of intercellular lipids would cause dramatic dilations between adherent cornified cells and enhance the penetration through the intercellular pathways. When the penetration of FITC-dextrans through Wistar rat skin was compared with that via hairless rat skin, the steady state flux of FITC-dextrans through Wistar rat skin pretreated with water-immiscible enhancers was 1.2- to 4.9-fold higher, suggesting that the penetration of large polar molecules through follicles may play at least some role in the percutaneous absorption.

Keywords: Alcohol, Ethyl/PHARMACOLOGY Animal Azepines/PHARMACOLOGY Ceramides/CHEMISTRY Dextrans/*PHARMACOKINETICS Epidermis/CHEMISTRY/METABOLISM Fluorescein-5-isothiocyanate/*ANALOGS & DERIVATIVES/ PHARMACOKINETICS In Vitro Lipids/CHEMISTRY Male Menthol/ANALOGS & DERIVATIVES/PHARMACOLOGY Myristates/PHARMACOLOGY Oleic Acids/PHARMACOLOGY Pharmaceutic Aids/*PHARMACOLOGY Rats Rats, Wistar Skin/CHEMISTRY Skin Absorption/*DRUG EFFECTS Sphingolipids/CHEMISTRY JOURNAL ARTICLE

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