title: In silico prediction of percutaneous absorption and disposition kinetics of chemicals.
abstract: OBJECTIVE
  To develop in-silico model for predicting percutaneous absorption and disposition kinetics of chemicals in skin layers so as to facilitate the design of transdermal drug delivery systems and skin care products, and risk assessment of occupational or consumer exposure.
  
  
  METHODS
  A general-purpose computer model for simulating skin permeation, absorption and disposition kinetics in the stratum corneum, viable dermis and dermis has been developed. Equations have been proposed for determining the partition and diffusion properties of chemicals by considering molecular partition, binding and mobility in skin layers. In vitro skin penetration data of 12 chemicals was used to validate the model.
  
  
  RESULTS
  The observed and simulated permeation and disposition in skin layers were compared for 12 tested chemicals. For most tested chemicals, the experimental and model results are in good agreement with the coefficient of determination >0.80 and relative root mean squared error <1.20. The disposition kinetic parameters of the maximum concentration and the area under the curve in the viable epidermis and dermis initially increased with hydrophobicity, but reached maxima and then decreased with further increase of hydrophobicity.
  
  
  CONCLUSIONS
  By considering skin physiological structure and composition, the partition and diffusion properties of chemicals in skin layers are determined. This allows in-silico simulation of percutaneous permeation, absorption and disposition kinetics of wide chemical space. The model produced results in good agreement with experimental data of 12 chemicals, suggesting a much improved framework to support transdermal delivery of drug and cosmetic actives as well as integrated risk assessment.
authors.affiliation: College of Engineering, China Agricultural University (East Campus), P.O. Box 191, 17 Qing-Hua-Dong-Lu, Beijing, 100083, People's Republic of China.
authors.forename: Longjian
authors.initials: L
authors.lastname: Chen
authors.forename: Lujia
authors.initials: L
authors.lastname: Han
authors.forename: Ouarda
authors.initials: O
authors.lastname: Saib
authors.forename: Guoping
authors.initials: G
authors.lastname: Lian
mesh_terms: D000279:Administration, Cutaneous; D003198:Computer Simulation; D020405:Dermis / Q000378:metabolism; D004058:Diffusion; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D004364:Pharmaceutical Preparations