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The Journal of investigative dermatology

Solute structure-permeability relationships in human stratum corneum.


PMID 2754277

Abstract

The permeability coefficients (kp) of a series of methyl-substituted p-cresols were determined in human stratum corneum along with their partition coefficients (PC) between water and untreated stratum corneum, delipidized stratum corneum, octanol, and heptane. The PC values were identical in untreated and delipidized stratum corneum, suggesting that the stratum corneum/water PC data reflect the protein domain rather than the lipids. Although uptake into human stratum corneum was relatively insensitive to solute lipophilicity, reflecting the predominant role of proteins in the uptake, permeability coefficients were found to be more sensitive to lipophilicity, suggesting that transport is by a lipid pathway. A log-log plot of kp versus stratum corneum/water PC within the phenol series is linear, but with a slope of 3.6, indicating that kp is not directly proportional to PC. Functional group contributions to the free energy of the transfer process reflected in permeability or partitioning experiments were compared with group contribution data generated previously for the same substituents attached to the chain terminus of 21-esters of hydrocortisone. Within experimental error, a given functional group altered permeability by the same factor in either series of compounds. Group contributions of polar, hydrogen bonding substituents obtained from kp data were similar to those from octanol/water PC data, suggesting that the barrier microenvironment resembles that of a hydrogen bonding organic solvent. Comparison of the kp values of substituted p-cresols with those of hydrocortisone esters having similar lipophilicities also indicated a steep dependence of kp on molecular weight (log kp = constant + psi log PC - n log MW, n = 4.6) similar to the dependence observed in other biomembranes and isolated lipid bilayers.

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