An experimentally based approach for predicting skin permeability of chemicals and drugs using a membrane-coated fiber array


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Abstract

A membrane-coated fiber (MCF) array approach is proposed for predicting the percutaneous absorption of chemicals and drugs from chemical or biological mixtures. Multiple MCFs were used to determine the partition coefficients of compounds (logKMCF). We hypothesized that one MCF will characterize one pattern of molecular interactions and therefore the skin absorption process can be simulated by a multiple MCF array having diverse patterns of molecular interactions. Three MCFs, polydimethylsiloxane (PDMS), polyacrylate (PA) and CarboWax (Wax), were used to determine the logKMCF values for a set of calibration compounds. The skin permeability log(kp) of the compounds was measured by diffusion experiments using porcine skin. The feasibility of the MCF array approach for predicting skin permeability was demonstrated with the three MCFs. A mathematical model was established by multiple linear regression analysis of the log(kp) and logKMCF data set: log(kp) = −2.34–0.124 logKpdms + 1.91 logKpa − 1.17 logKwax (n = 25, R2 = 0.93). The MCF array approach is an alternative animal model for skin permeability measurement. It is an experimentally based, high throughput approach that provides high prediction confidence and does not require literature data nor molecular structure information in contrast to the existing predictive models.

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