Rat epidermal keratinocyte organotypic culture (ROC) compared to human cadaver skin: the effect of skin permeation enhancers.
The objective of this study was to evaluate the response of the rat epidermal keratinocyte organotypic culture (ROC) to permeation enhancers, and to compare these responses to those in human cadaver skin. Different concentrations of two mixtures for enhancing permeation were investigated, sodium dodecyl sulfate:phenyl piperazine and methyl pyrrolidone:dodecyl pyridinium chloride, using skin impedance spectroscopy and two experimental compounds, the lipophilic corticosterone and the hydrophilic sucrose. The chemical irritation effects of the formulations were evaluated based on leakage of lactate dehydrogenase enzyme (LDH) and cellular morphological perturbation. This study provides evidence for direct correlations of permeation/permeation, impedance/impedance and permation/impedance between the culture model and human skin. The only exception was the enhancer induced permeation of sucrose which was 1-40-fold higher in ROC compared to human skin, reflecting the more disordered lipid organization in stratum corneum and consequently the greater number of polar pathways. LDH leakage and cellular morphology indicated that it was possible to differentiate between safe permeation enhancers from irritating agents. This is not only the first study to have compared the enhancer effects on a cultured skin model with human skin, but also it has demonstrated enhancer induced irritation using an artificial skin model.
Pappinen
Sari
S
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. sari.pappinen@uku.fi
Tikkinen
Sanna
S
Pasonen-Seppänen
Sanna
S
Murtomäki
Lasse
L
Suhonen
Marjukka
M
Urtti
Arto
A
D000287:Administration, Topical; D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D002102:Cadaver; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003345:Corticosterone / Q000008:administration & dosage / Q000493:pharmacokinetics; D017097:Electric Impedance; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007509:Irritants; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009924:Organ Culture Techniques; D010539:Permeability / Q000187:drug effects; D051381:Rats; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D013395:Sucrose / Q000008:administration & dosage / Q000493:pharmacokinetics
D007509:Irritants; D013395:Sucrose; D007770:L-Lactate Dehydrogenase; D003345:Corticosterone