The role of corneocytes in skin transport revised-a combined computational and experimental approach

Steffi Hansen, Arne Naegel, Michael Heisig, Gabriel Wittum, Dirk Neumann, Karl Heinz Kostka, Peter Meiers, Claus Michael Lehr, Ulrich F. Schaefer

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Purpose: To investigate mechanisms of compound-corneocyte interactions in a combined experimental and theoretical approach. Materials and Methods: Experimental methods are presented to investigate compound-corneocyte interactions in terms of dissolution within water of hydration and protein binding and to quantify the extent of the concurrent mechanisms. Results are presented for three compounds: caffeine, flufenamic acid, and testosterone. Two compartmental stratum corneum models M1 and M2 are formulated based on experimentally determined input parameters describing the affinity to lipid, proteins and water. M1 features a homogeneous protein compartment and considers protein interactions only via intra-corneocyte water. In M2 the protein compartment is sub-divided into a cornified envelope compartment interacting with inter-cellular lipids and a keratin compartment interacting with water. Results: For the non-protein binding caffeine the impact of the aqueous compartment on stratum corneum partitioning is overestimated but is successfully modeled after introducing a bound water fraction that is non-accessible for compound dissolution. For lipophilic, keratin binding compounds (flufenamic acid, testosterone) only M2 correctly predicts a concentration dependence of stratum corneum partition coefficients. Conclusions: Lipophilic and hydrophilic compounds interact with corneocytes. Interactions of lipophilic compounds are probably confined to the corneocyte surface. Interactions with intracellular keratin may be limited by their low aqueous solubility.

Original languageEnglish (US)
Pages (from-to)1379-1397
Number of pages19
JournalPharmaceutical Research
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • Compartmental model
  • Dual-sorption theory
  • Langmuir isotherm
  • Partition coefficient
  • Skin

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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