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  • Title: Heterogeneity effects on permeability-partition coefficient relationships in human stratum corneum.
    Author: Anderson BD, Higuchi WI, Raykar PV.
    Journal: Pharm Res; 1988 Sep; 5(9):566-73. PubMed ID: 3247319.
    Abstract:
    The relationship between the permeability of solutes undergoing transport via the lipid pathway of the stratum corneum and the degree to which the same solutes partition into the stratum corneum has been explored by measuring the permeability coefficients and stratum corneum/water partition coefficients of a series of hydrocortisone esters varying in lipophilicity. Isolated human stratum corneum, used in both the permeability and the uptake experiments, was shown to resemble full-thickness skin in its overall resistance and selectivity to solute structure. As with full-thickness skin, delipidization destroys the barrier properties of isolated stratum corneum. Although a linear relationship is frequently assumed to exist between permeability coefficients and membrane/water partition coefficients, a log-log plot of permeability coefficients versus the intrinsic stratum corneum/water partition coefficients for the series of hydrocortisone esters studied is distinctly nonlinear. This nonlinearity arises from the fact that the transport of these solutes is rate limited by a lipid pathway in the stratum corneum, while uptake reflects both lipid and protein domains. From the relative permeability coefficients of 21-esters of hydrocortisone varying in acyl-chain structure, group contributions to the free energy of transfer of solute into the rate-limiting barrier microenvironment of the stratum corneum lipid pathway are calculate for a variety of functional groups including the -CH2-, -CONH2, -CON(CH3)2, -COOCH3, -COOH, and -OH groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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