The Influence of Various Freezing-thawing Methods of Skin on Drug Permeation and Skin Barrier Function.

IF 5 3区 医学 Q1 PHARMACOLOGY & PHARMACY AAPS Journal Pub Date : 2024-07-02 DOI:10.1208/s12248-024-00941-7
Xinying Wang, Yuanyuan Zhang, Kaili Liang, Xue Meng, Chunyan Ma, Qing Wang
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Abstract

The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing-thawing processes on the barrier function of skin and the transdermal permeability of granisetron and lidocaine. Rat and hairless mouse skins were thawed at three different conditions after being frozen at -20℃ for 9 days: thawed at 4℃, room temperature (RT), and 32℃. There were no significant differences in the steady-state fluxes of drugs between fresh and thawed samples, but compared with fresh skin there were significant differences in lag time for the permeation of granisetron in rat skins thawed at RT and 32℃. Histological research and scanning electron microscopy images showed no obvious structural damage on frozen/thawed skin, while immunohistochemical staining and enzyme-linked immunosorbent assay for the tight junction (TJ) protein Cldn-1 showed significantly impaired epidermal barrier. It was concluded that the freezing-thawing process increases the diffusion rate of hydrophilic drugs partly due to the functional degradation of TJs. It's recommended that hairless, inbred strains and identical animal donors should be used, and the selected thawing method of skin should be validated prior to IVPT, especially for hydrophilic drugs.

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各种皮肤冻融方法对药物渗透和皮肤屏障功能的影响
皮肤的选择对于体外渗透试验(IVPT)至关重要。本研究旨在探讨不同冻融过程对皮肤屏障功能以及格拉司琼和利多卡因透皮渗透性的影响。大鼠和无毛小鼠的皮肤在-20℃冷冻9天后在三种不同条件下解冻:4℃解冻、室温(RT)解冻和32℃解冻。新鲜样本和解冻样本的药物稳态通量无明显差异,但与新鲜皮肤相比,格拉司琼在室温和 32℃ 解冻的大鼠皮肤中的渗透滞后时间有明显差异。组织学研究和扫描电子显微镜图像显示,冷冻/解冻的皮肤没有明显的结构损伤,而免疫组化染色和酶联免疫吸附法检测紧密连接(TJ)蛋白 Cldn-1 则显示表皮屏障明显受损。结论是冻融过程增加了亲水性药物的扩散速度,部分原因是 TJ 的功能退化。建议使用无毛、近交系和相同的动物供体,并在 IVPT 之前验证所选的皮肤解冻方法,尤其是亲水性药物。
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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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