Quantitative structure-skin permeability relationships

Abstract

Quantitative Structure -Skin permeability Relationships http://researchonline.ljmu.ac.uk/6719/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription. This paper reviews in silico models currently available for the prediction of skin permeability with the main focus on the quantitative structure-permeability relationship (QSPR) models. A comprehensive analysis of the main achievements in the field in the last decade is provided. In addition, the mechanistic models are discussed and comparative studies that analyse different models are discussed. (to be extended to 100--200 words)

Predicting Skin Permeability by Means of Computational Approaches: Reliability and Caveats in Pharmaceutical Studies

“…A compound can permeate the stratum corneum by the intercellular, transcellular or appendageal routes, according to its size and its chemico-physical properties 5,6 . Skin permeability is widely recognized as an essential parameter to be considered for the delivery of active substances 1 , but it is also considered important for risk assessment purposes 7 . Guidelines for in vitro and in vivo skin permeation tests have been drafted by the OECD 8,9 , but no universal protocol has been developed.…”

“…Moreover, it is impossible to evaluate compounds not yet synthetized. Hence, it is crucial to use an efficient and accurate in silico model of human skin permeability in order to reduce product development costs in early stage screening 10 , resolve ethical issues, understand the 2 mechanisms of absorption 1 , and reduce measurements variability. In fact, it has been shown that the skin permeability can variate inter-and intra-subject 11 .…”

“…It consists of three separate and diverse layers, each one with a distinct cellular composition, characteristic, and function: epidermis, dermis and hypodermis. The outermost layer, epidermis, is formed of the viable epidermis and non-viable stratum corneum, which provides the main barrier to permeation and is considered as the "rate-limiting step of permeation" 1 . The stratum corneum is a specialized tissue type, whose main function is to control the absorption of substances into the skin and to maintain the fluid homeostasis.…”

In silico prediction of dermal absorption of pesticides – an evaluation of selected models against results from in vitro testing

“…through extraction or fluidization of the lipid bilayer) or could cause irritation and/or corrosion. A step forward in that direction could be the examination of models developed specifically for transdermal enhancers, as discussed in Tsakovska [53]. Unfortunately, these latter approaches could not be examined against our dataset due to a lack of detailed information on formulation composition, which is usually treated as confidential business information in the case of plant protection products.…”

Ab initio chemical safety assessment: A workflow based on exposure considerations and non-animal methods

“…Physicochemical properties such as the molecular weight and partition coefficients (log P) may inform possible penetration through skin and other tissues. Several QSPRs (Quantitative Structure-Property-Relationships) for skin penetration have been developed on this basis (Dumont et al [16] , recent review of computational skin permeability models: Tsakovska et al [90] ). Volatility must be considered in the exposure scenario and determination made of whether it is possible to exclude intake through inhalation.…”