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

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A Framework for Incorporating Transient Solute-Keratin Binding Into Dermal Absorption Models.

Johannes M Nitsche1, Gerald B Kasting2

  • 1Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, United States.

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This study models solute binding to keratin, revealing how lipophilicity affects topical compound absorption through skin. Understanding these binding dynamics quantifies the skin

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Area of Science:

  • Pharmacokinetics and biophysics
  • Skin permeation and drug delivery
  • Materials science of keratin interactions

Background:

  • Topical compound absorption through human stratum corneum is influenced by solute binding to keratin.
  • Previous models analyzed solute binding but lacked multi-level homogenization.
  • Understanding binding kinetics is crucial for predicting topical drug efficacy.

Purpose of the Study:

  • To analyze transient solute binding to keratin substrates.
  • To model the impact of binding on topical compound permeation through stratum corneum.
  • To develop quantitative methods for estimating skin reservoir function.

Main Methods:

  • Extended an earlier model with a second homogenization level (ultrascopic-to-microscopic).
  • Analyzed binding in isolated keratin suspensions (ultrascopic) and corneocyte interiors (microscopic).
  • Focused on linear binding isotherms common in dilute solutions.

Main Results:

  • Identified a maximum in the macroscopic forward binding rate constant related to solute lipophilicity.
  • Observed monotonic increases in the equilibrium constant and decreases in the macroscopic reverse binding rate constant.
  • Found that stratum corneum hydration affects the location and size of the binding maximum.

Conclusions:

  • Developed explicit equations linking keratin binding data to skin absorption kinetics.
  • Enabled more quantitative estimation of the stratum corneum's reservoir function.
  • Provided a framework for predicting topical compound permeation based on solute-keratin interactions.