A novel in vitro percutaneous penetration model: evaluation of barrier properties with p-aminobenzoic acid and two of its derivatives.
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.
de Jager
Miranda
M
Department of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, PO Box 9052, 2300 RA Leiden, The Netherlands.
Groenink
Wouter
W
Bielsa i Guivernau
Ruth
R
Andersson
Elin
E
Angelova
Nadezhda
N
Ponec
Maria
M
Bouwstra
Joke
J
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
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