Animal skin, chemical permeability

Permeability coefficients may be affected by chemical properties other than log and MW. For example, steric interactions, limitations of MW as a representation of molecular size, and unidentified factors that cause some compounds to act as penetration enhancers may affect permeability coefficients but would not be conveyed entirely by log and MW. Equation 15.7 will not account for these additional influences on permeability coefficients. However, the error in Equation 15.8 may be reduced compared with Equation 15.7, because Equation 15.8 is based on the animal-to-human ratio of permeabihty values. Equation 15.7 implicitly assumes that permeability coefficients are affected by log and MW only, which is a more restrictive assumption than the assumption built into Equation 15.8 that all unexplored factors have quantitatively the same effect in all species. That is, with the same amount of data, analysis with Equation 15.8 is preferable to analysis with Equation 15.7 as long as these additional factors influence permeability coefficients the same way in both human and animal skins. 

New databases were created consisting of chemicals for which fully validated measurements appeared in both the animal and human skin data sets. For compounds with multiple measurements, each measurement was independently adjusted for ionization (if necessary), and then all adjusted measurements for that compound were averaged. The ratio of the average animal and average human permeability coefficients was then calculated for each compound in the database of common chemicals. The logarithm of the ratios of the animal-to-human permeability coefficients were then linearly regressed as a function of MW and log using Equation 15.8. For all the databases studied here, the effects of both MW and log were... 

Before administration of the test substance, selected healthy, young adult animals are acclimated to laboratory conditions for at least 5 days. Before the test, animals are randomized and assigned to treating groups. Approximately 24 hours before the test, the fur on the skin should be clipped or shaved from the dorsal area of the trunk of the test animal. Care must be taken to avoid abrading the skin, which could alter the permeability of the test chemical through the skin. Approximately 10% of the body surface area should be prepared for application of the test chemical. 

A variety of chemical penetration enhancers with or without protease inhibitors or colloidal vehicles (liposomes) have been investigated for their potential to enhance the skin permeability of peptides and pro-teins, but these approaches have only been limited to animal models or in vitro or in vivo models of human skin and have not progressed to human clinical studies. A notable exception is the use of so-called Transferosomes , ultraflexible liposomes, containing a mixture of soybean phosphatidylcholine and sodium... 

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