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Percutaneous Penetration and Metabolism of Ketoprofen Isopropyl Ester Through a Tissue Engineering Skin Reconstructed with HaCaT Cells and Its Molecule Mechanism

Author: XuYanFeng
Tutor: HuJinHong
School: Second Military Medical University
Course: Pharmacology
Keywords: Tissue-engineered skin Human carboxylesterase 2 Ketoprofen Ketoprofen isopropyl Stereoselective metabolism
CLC: R96
Type: PhD thesis
Year: 2005
Downloads: 123
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Abstract

Become one of the priorities of the research and development of the third generation of pharmaceutical preparations for its unique advantages of transdermal drug delivery system, developing very rapidly. Animals (rats, pigs, etc.) skin or human cadaver skin penetration and metabolism studies in vitro percutaneous absorption usually, there is a big difference but they are healthy human skin structure, physiological, tissue-engineered skin become healthy human skin substitute research focus. The tissue-engineered skin is usually used to build healthy human skin cells freshly isolated due to limited sources of healthy human skin, and the differences between the donor can lead to different cells, so the method is to build the application of tissue-engineered skin has been largely restricted. Cell lines can solve the source of the problem of skin cells, but also can improve the reproducibility of the tissue-engineered skin. Skin is the largest organ of the human body, and over the years, has always been considered to be passive barrier between the environment and the body structure, but more and more research results show that the skin is an active metabolic organ, the expression of a variety of metabolic enzyme, a variety of endogenous and exogenous substances biotransformation to play a crucial role. Use of the metabolism of the skin esterase and the like, can directly the lipophilic drug metabolism hydrophilic drugs, which influence percutaneous absorption of the drug, therefore, when the prodrug of the design of percutaneous administration, a lipophilic drug, the biological transformation rate is a important considerations. Original drug modified to have an ester bond, the prodrugs of the amide bond structure of the original drug can be improved lipophilicity, increase the percutaneous drug permeation amount. The subject by normal human abdominal epidermal keratinocytes derived from HaCaT keratinocyte cell line and dermal fibroblasts sources vitro construct tissue engineered skin as a model drug, ketoprofen isopropyl research such skin percutaneous penetration and metabolic, molecular cloning techniques to study the mechanism of ketoprofen selective metabolism of iso-propyl percutaneous penetration process. We first formed epidermal keratinocyte cell line HaCaT cells and human dermal fibroblast cells sources, extracted the type Ⅰ bovine collagen dermal matrix embedding fibroblasts, HaCaT cells inoculated on the gas - liquid interface culture for 4 weeks observe the impact of different culture media on the tissue-engineered skin, HE stained sections observed morphology of cultured skin structure. Was found in HaCaT cells by gas - liquid interface culture can form the class of the epidermis, but can not form a complete cuticle. Vit C can significantly promote cell proliferation, Vit D ₃ promote cell differentiation, estradiol this tissue-engineered skin had no significant effect.

Percutaneous Penetration and Metabolism of Ketoprofen Isopropyl Ester Through a Tissue Engineering Skin Reconstructed with HaCaT Cells and Its Molecule Mechanism

Abstract

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