title: A novel in vitro percutaneous penetration model: evaluation of barrier properties with p-aminobenzoic acid and two of its derivatives.
abstract: OBJECTIVE
  The objective of this study was to evaluate the utility of a stratum corneum substitute (SCS) as a novel in vitro percutaneous penetration model. The SCS consists of synthetic stratum corneum (SC) lipids (cholesterol, free fatty acids, and specific ceramides) applied onto a porous substrate. The composition, organization, and orientation of lipids in the SCS bear high resemblance to that of the intercellular barrier lipids in SC.
  
  
  METHODS
  The barrier integrity of the SCS was evaluated by means of passive diffusion studies, using three model compounds with different lipophilicities. The effects of lipid layer thickness, permeant lipophilicity, and altered lipid composition on the barrier properties were investigated, using isolated human SC as a control sample.
  
  
  RESULTS
  For all three model compounds, the permeability characteristics of the SCS with a 12-mum-thick lipid layer closely resemble those of human SC. Modification of the lipid composition, generating an SCS that lacks the characteristic long periodicity phase as present in SC, was accompanied by a 2-fold increased permeability.
  
  
  CONCLUSIONS
  The SCS offers an attractive tool to predict solute permeation through human skin. Moreover, as its lipid composition can be modified, they may also serve as a suitable screening model for diseased skin.
authors.affiliation: Department of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, PO Box 9052, 2300 RA Leiden, The Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: de Jager
authors.forename: Wouter
authors.initials: W
authors.lastname: Groenink
authors.forename: Ruth
authors.initials: R
authors.lastname: Bielsa i Guivernau
authors.forename: Elin
authors.initials: E
authors.lastname: Andersson
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Angelova
authors.forename: Maria
authors.initials: M
authors.lastname: Ponec
authors.forename: Joke
authors.initials: J
authors.lastname: Bouwstra
mesh_terms: D010129:4-Aminobenzoic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000279:Administration, Cutaneous; D001566:Benzocaine / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002518:Ceramides / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D004817:Epidermis / Q000378:metabolism* / Q000648:ultrastructure; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D012869:Skin Absorption; D013473:Sunscreening Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D062366:para-Aminobenzoates
chemical_list: D002518:Ceramides; D005230:Fatty Acids, Nonesterified; D008051:Lipid Bilayers; D013473:Sunscreening Agents; D062366:para-Aminobenzoates; C030553:4-n-butylaminobenzoic acid; D002784:Cholesterol; D010129:4-Aminobenzoic Acid; D001566:Benzocaine