Senpei Yang1, Lingyi Li1, Tao Chen2, Lujia Han3, Guoping Lian4,5. 1. China Agricultural University, P.O. Box 191, 17 Qing-Hua-Dong-Lu, Beijing, 100083, China. 2. University of Surrey, Guildford, GU27XH, UK. 3. China Agricultural University, P.O. Box 191, 17 Qing-Hua-Dong-Lu, Beijing, 100083, China. hanlj@cau.edu.cn. 4. University of Surrey, Guildford, GU27XH, UK. guoping.lian@unilever.com. 5. Unilever Research Colworth, Colworth Park, Sharnbrook, Bedfordshire, MK401LQ, UK. guoping.lian@unilever.com.
Abstract
PURPOSE: Sebum is an important shunt pathway for transdermal permeation and targeted delivery, but there have been limited studies on its permeation properties. Here we report a measurement and modelling study of solute partition to artificial sebum. METHODS: Equilibrium experiments were carried out for the sebum-water partition coefficients of 23 neutral, cationic and anionic compounds at different pH. RESULTS: Sebum-water partition coefficients not only depend on the hydrophobicity of the chemical but also on pH. As pH increases from 4.2 to 7.4, the partition of cationic chemicals to sebum increased rapidly. This appears to be due to increased electrostatic attraction between the cationic chemical and the fatty acids in sebum. Whereas for anionic chemicals, their sebum partition coefficients are negligibly small, which might result from their electrostatic repulsion to fatty acids. Increase in pH also resulted in a slight decrease of sebum partition of neutral chemicals. CONCLUSIONS: Based on the observed pH impact on the sebum-water partition of neutral, cationic and anionic compounds, a new quantitative structure-property relationship (QSPR) model has been proposed. This mathematical model considers the hydrophobic interaction and electrostatic interaction as the main mechanisms for the partition of neutral, cationic and anionic chemicals to sebum.
PURPOSE: Sebum is an important shunt pathway for transdermal permeation and targeted delivery, but there have been limited studies on its permeation properties. Here we report a measurement and modelling study of solute partition to artificial sebum. METHODS: Equilibrium experiments were carried out for the sebum-water partition coefficients of 23 neutral, cationic and anionic compounds at different pH. RESULTS: Sebum-water partition coefficients not only depend on the hydrophobicity of the chemical but also on pH. As pH increases from 4.2 to 7.4, the partition of cationic chemicals to sebum increased rapidly. This appears to be due to increased electrostatic attraction between the cationic chemical and the fatty acids in sebum. Whereas for anionic chemicals, their sebum partition coefficients are negligibly small, which might result from their electrostatic repulsion to fatty acids. Increase in pH also resulted in a slight decrease of sebum partition of neutral chemicals. CONCLUSIONS: Based on the observed pH impact on the sebum-water partition of neutral, cationic and anionic compounds, a new quantitative structure-property relationship (QSPR) model has been proposed. This mathematical model considers the hydrophobic interaction and electrostatic interaction as the main mechanisms for the partition of neutral, cationic and anionic chemicals to sebum.
Authors: Laura J van 't Veer; Hongyue Dai; Marc J van de Vijver; Yudong D He; Augustinus A M Hart; Mao Mao; Hans L Peterse; Karin van der Kooy; Matthew J Marton; Anke T Witteveen; George J Schreiber; Ron M Kerkhoven; Chris Roberts; Peter S Linsley; René Bernards; Stephen H Friend Journal: Nature Date: 2002-01-31 Impact factor: 49.962