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Related Experiment Videos

Solute structure-permeability relationships in human stratum corneum.

B D Anderson1, P V Raykar

  • 1Department of Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City 84108.

The Journal of Investigative Dermatology
|August 1, 1989
PubMed
Summary

Skin permeability depends on both protein and lipid interactions. While protein binding influences uptake, lipid pathways dominate transport, with molecular weight significantly impacting permeability across biological membranes.

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Area of Science:

  • Dermal penetration and drug delivery
  • Biophysical chemistry
  • Stratum corneum biophysics

Background:

  • The stratum corneum (SC) is the primary barrier to transdermal drug absorption.
  • Understanding SC permeability is crucial for developing effective topical and transdermal therapies.
  • Solute partitioning and diffusion within the SC are complex processes influenced by its heterogeneous composition.

Purpose of the Study:

  • To investigate the relationship between partition coefficients (PC) and permeability coefficients (kp) in human stratum corneum.
  • To elucidate the roles of proteins and lipids in solute uptake and transport across the SC.
  • To compare functional group contributions to permeability and partitioning across different molecular series.

Main Methods:

  • Determination of permeability coefficients (kp) for methyl-substituted p-cresols in human stratum corneum.

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  • Measurement of partition coefficients (PC) between SC (untreated and delipidized) and water, octanol, and heptane.
  • Analysis of log-log plots of kp versus SC/water PC and comparison with existing data for hydrocortisone esters.

    • Main Results:

    • Partition coefficients in untreated and delipidized SC were identical, indicating SC/water PC reflects protein interactions.
    • Solute uptake into SC was insensitive to lipophilicity, but permeability coefficients (kp) were sensitive, suggesting lipid pathway dominance.
    • Permeability showed a steep dependence on molecular weight (n=4.6), consistent with other biomembranes.

    Conclusions:

    • The SC barrier involves both protein-mediated uptake and lipid-mediated transport.
    • Functional group contributions to permeability are consistent across different chemical series.
    • The SC microenvironment shares characteristics with hydrogen-bonding organic solvents.