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  • In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities.

In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities.

Journal of medicinal chemistry (2007-02-16)
Giorgio Ottaviani, Sophie Martel, Pierre-Alain Carrupt
ABSTRACT

The development of in silico and in vitro tools to estimate or predict the passive human skin permeation and distribution of new chemical entities, useful in dermal drug delivery, in absorption studies of toxic compounds, and in the cosmetics industry, is presented. In vitro permeation parameters were measured using the artificial membrane PAMPA-skin. The Volsurf approach was then applied to extract pertinent descriptors from molecular interaction fields characterizing the molecular structure of tested compounds. Two useful three-dimensional solvatochromic models able to predict PAMPA permeation parameters directly from the molecular structure were obtained using the partial least squares analysis. The models also provide valuable information to understand the link between physicochemical and structural properties of tested compounds and their interactions with the artificial membrane PAMPA-skin and can be useful to rapidly estimate their permeation through the human skin.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Resorcinol, ≥98%, FG
Sigma-Aldrich
4-Chlorophenol, ≥99%
Sigma-Aldrich
4-Phenylbutyric acid, 99%
Sigma-Aldrich
Isoquinoline, 97%
Sigma-Aldrich
Resorcinol, ACS reagent, ≥99.0%
Sigma-Aldrich
N,N-Diethylaniline, ≥99%
Sigma-Aldrich
3,4-Dimethylphenol, 98%
Sigma-Aldrich
4-Ethylphenol, ≥98%, FG
Supelco
Sulfadimethoxine, VETRANAL®, analytical standard
Sigma-Aldrich
Methyl nicotinate, puriss., ≥99.0% (GC)
Supelco
(−)-Nicotine, PESTANAL®, analytical standard
Supelco
Progesterone, VETRANAL®, analytical standard
Sigma-Aldrich
Methyl nicotinate, 99%
Sigma-Aldrich
o-Cresol, ≥99%
Supelco
Sulfanilamide, VETRANAL®, analytical standard
Sigma-Aldrich
Corticosterone, ≥98.5% (HPLC)
Sigma-Aldrich
4-Ethylphenol, 99%
Sigma-Aldrich
3,4-Xylenol, ≥98%, FG
Sigma-Aldrich
Resorcinol, ReagentPlus®, 99%
Sigma-Aldrich
Lidocaine, powder
Sigma-Aldrich
Triamcinolone
Sigma-Aldrich
Lidocaine, analytical standard
Supelco
Sulfadimethoxine, 98.0-102.0%
Sigma-Aldrich
Resorcinol, BioXtra, ≥99%
Sigma-Aldrich
Progesterone, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
(−)-Nicotine, ≥99% (GC), liquid
Sigma-Aldrich
Hydrocortisone-Water Soluble, BioReagent, suitable for cell culture
Sigma-Aldrich
Indomethacin, 98.5-100.5% (in accordance with EP)
Sigma-Aldrich
Corticosterone, ≥92%