Penetration and distribution of three lipophilic probes in vitro in human skin focusing on the hair follicle

被引:48
作者
Grams, YY [1 ]
Bouwstra, JA [1 ]
机构
[1] Leiden Univ, Dept Pharmaceut Technol, Leiden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands
关键词
hair follicle; relative quantification; confocal laser scanning microscopy; permeant lipophilicity; accumulation;
D O I
10.1016/S0168-3659(02)00205-5
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Fluorescent model substances of increasing lipophilicity (Oregon Green(R) 488, Bodipy(R), FL C-5 and Bodipy(R) 564/570 C-5) were selected to enable the visualization in the skin using confocal laser scanning microscopy. After measuring the penetration for 18 h, the nonfixed human scalp skin was imaged from the bottom parallel to the stratum corneum and in a cross-section view perpendicular to the skin surface. The images were evaluated by calculating relative accumulation values for different penetrants. The studies indicate that the penetrated amount is highest for Bodipy FL CS (medium lipophilicity) and lowest for Bodipy 564/570 CS (high lipophilicity) whereas Bodipy(R) 564/570 CS (high lipophilicity) reveals the highest relative accumulation in parts of the hair follicle compared to Oregon Green 488 (low lipophilicity). The addition of 30% (v/v) ethanol to the donor phase of substance with a low lipophilicity increases the follicular delivery. From our results we conclude that delivery to the hair follicle can be improved by increasing the drugs lipophilicity and optimizing the composition of the donor phase. However, no conclusion can be drawn about the actual route of transport to the hair follicle. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:253 / 262
页数:10
相关论文
共 27 条
[1]   The pilosebaceous unit: A pivotal route for topical drug delivery [J].
Agarwal, R ;
Katare, OP ;
Vyas, SP .
METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY, 2000, 22 (02) :129-133
[2]   ROLE OF THE APPENDAGEAL PATHWAY IN THE PERCUTANEOUS-ABSORPTION OF PYRIDOSTIGMINE BROMIDE IN VARIOUS VEHICLES [J].
BAMBA, FL ;
WEPIERRE, J .
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, 1993, 18 (04) :339-348
[3]  
Berner B., 1995, PERCUTANEOUS PENETRA, P45
[4]   THE EFFECTS OF ETHANOL ON THE TRANSPORT OF LIPOPHILIC AND POLAR PERMEANTS ACROSS HAIRLESS MOUSE SKIN - METHODS VALIDATION OF A NOVEL-APPROACH [J].
GHANEM, AH ;
MAHMOUD, H ;
HIGUCHI, WI ;
LIU, PC ;
GOOD, WR .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1992, 78 (2-3) :137-156
[5]   A new method to determine the distribution of a fluorophore in scalp skin with focus on hair follicles [J].
Grams, YY ;
Bouwstra, JA .
PHARMACEUTICAL RESEARCH, 2002, 19 (03) :350-354
[6]  
Hashimoto K., 1976, BIOL DISEASE HAIR, P2357
[7]   ROLE OF TRANSEPIDERMAL AND TRANSFOLLICULAR ROUTES IN PERCUTANEOUS-ABSORPTION OF STEROIDS - IN-VITRO STUDIES ON HUMAN SKIN [J].
HUEBER, F ;
SCHAEFER, H ;
WEPIERRE, J .
SKIN PHARMACOLOGY, 1994, 7 (05) :237-244
[8]   PERCUTANEOUS-ABSORPTION OF ESTRADIOL AND PROGESTERONE IN NORMAL AND APPENDAGE-FREE SHIN OF THE HAIRLESS RAT - LACK OF IMPORTANCE OF NUTRITIONAL BLOOD-FLOW [J].
HUEBER, F ;
BESNARD, M ;
SCHAEFER, H ;
WEPIERRE, J .
SKIN PHARMACOLOGY, 1994, 7 (05) :245-256
[9]  
Illel B, 1997, CRIT REV THER DRUG, V14, P207
[10]  
KEISTER J C, 1986, Journal of Controlled Release, V4, P111, DOI 10.1016/0168-3659(86)90046-5