[Percutaneous penetration of ketoprofen and ketoprofen isopropyl ester through a tissue engineering skin reconstructed with HaCaT cells].
OBJECTIVE
To reconstruct of a tissue engineering skin in vitro for the study of the use of drug percutaneous penetration and metabolism.


METHODS
Dermal fibroblasts were embedded in collagen type I. HaCaT cells were seeded on the top of the gel. The skin was generated through air-liquid interface culture. Effects of various culture media on tissues morphology were investigated. Sections of the cultured skin were stained with hematoxylin and eosin and examined under microscope. Permeation and metabolism of ketoprofen and its isopropyl ester through the cultured skin were investigated.


RESULTS
HaCaT cells initially developed a multilayer epithelium at the air-liquid interface, but it showed a parakeratotic stratum corneum. Vitamin C enhanced cell proliferation obviously. Vitamin D3 promoted cell differentiation. And estradiol showed little effect on the tissue engineering skin. Ketoprofen isopropyl ester was hydrolyzed into ketoprofen when penetrated through the cultured skin, which resembled in the skin cell homogenates metabolism.


CONCLUSIONS
Cultured at the air-liquid interface, HaCaT cells developed a parakeratotic mutilayer epithelium. Enzyme activity was reserved. This cultured skin could serve as an appropriate model for drug percutaneous metabolism and skin irritation.
Xu
Yan-Feng
YF
Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Hu
Jin-Hong
JH
Zhu
Quan-Gang
QG
Xu
Shu
S
Pan
Yong-Hua
YH
D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D004952:Esters / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006367:HeLa Cells / Q000166:cytology; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004952:Esters; D007660:Ketoprofen