Does slowly reversible binding to keratin contribute to stratum corneum reservoir function?

Area of Science:

• Dermatology and Pharmaceutical Sciences
• Biophysics and Physical Chemistry
• Materials Science and Engineering

Background:

• The human stratum corneum (HSC) exhibits a reservoir function for topical chemicals, but its origin is unclear.
• Reversible binding to keratin is a proposed mechanism contributing to this storage capacity.

Purpose of the Study:

• To investigate the role of reversible keratin binding in the HSC reservoir function.
• To quantify the kinetics of chemical uptake and desorption from HSC.
• To compare experimental data with theoretical models of chemical-ligand interactions.

Main Methods:

• In vitro measurement of geraniol uptake and desorption from isolated and delipidized HSC.
• Analysis of literature data for testosterone and 1-propanol desorption.
• Comparison with theoretical models for homogeneous membranes with varying binding kinetics.
• Model-based calculations for corticosteroid retention in partially hydrated skin.

Main Results:

• Geraniol, testosterone, and 1-propanol data suggest slowly reversible binding within the HSC protein phase, with rapid desorption observed.
• Model calculations indicate significantly longer retention times (up to two weeks) for corticosteroids in partially hydrated skin.
• This suggests a combination of slow diffusion in the lipid phase and strong equilibrium binding in the protein phase for corticosteroids.

Conclusions:

• Slowly reversible binding in the protein phase contributes to the HSC reservoir function for many lipophilic chemicals.
• For corticosteroids, a combination of slow lipid diffusion and strong protein binding is the primary driver of prolonged retention.
• Understanding these mechanisms is crucial for optimizing topical drug delivery and efficacy.