title: The role of corneocytes in skin transport revised--a combined computational and experimental approach.
abstract: OBJECTIVE
  To investigate mechanisms of compound-corneocyte interactions in a combined experimental and theoretical approach.
  
  
  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.
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Hansen
authors.forename: Arne
authors.initials: A
authors.lastname: Naegel
authors.forename: Michael
authors.initials: M
authors.lastname: Heisig
authors.forename: Gabriel
authors.initials: G
authors.lastname: Wittum
authors.forename: Dirk
authors.initials: D
authors.lastname: Neumann
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Kostka
authors.forename: Peter
authors.initials: P
authors.lastname: Meiers
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Schaefer
mesh_terms: D001692:Biological Transport; D002110:Caffeine / Q000378:metabolism / Q000493:pharmacokinetics*; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005439:Flufenamic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007633:Keratins / Q000032:analysis / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008954:Models, Biological; D011485:Protein Binding; D012869:Skin Absorption; D012995:Solubility; D013739:Testosterone / Q000378:metabolism / Q000493:pharmacokinetics*; D014867:Water / Q000032:analysis / Q000378:metabolism
chemical_list: D008055:Lipids; D014867:Water; D002110:Caffeine; D013739:Testosterone; D005439:Flufenamic Acid; D007633:Keratins