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Tat 肽和弹性阳离子型尼莫司汀囊泡包封增强人酪氨酸酶质粒 (pAH7/Tyr) 的透皮吸收和稳定性。

Potent enhancement of transdermal absorption and stability of human tyrosinase plasmid (pAH7/Tyr) by Tat peptide and an entrapment in elastic cationic niosomes.

机构信息

Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.

出版信息

Drug Deliv. 2013;20(1):10-8. doi: 10.3109/10717544.2012.742937.

Abstract

Enhancement of transdermal absorption through rat skin and stability of the human tyrosinase plasmid (P) using Tat (T) and an entrapment in elastic cationic niosomes (E) were described. E (Tween61:cholesterol:DDAB at 1:1:0.5 molar ratio) were prepared by the freeze-dried empty liposomes (FDELs) method using 25% ethanol. TP was prepared by a simple mixing method. TPE was prepared by loading T and P in E at the T:P:E ratio of 0.5:1:160 w/w/w. For gel formulations, P, TP, PE and TPE were incorporated into Carbopol 980 gel (30 µg of plasmid per 1 g of gel). For the transdermal absorption studies, the highest cumulative amounts and fluxes of the plasmid in viable epidermis and dermis (VED) were observed from the TPE of 0.31 ± 0.04 µg/cm(2) and 1.86 ± 0.24 µg/cm(2)/h (TPE solution); and 4.29 ± 0.40 µg/cm(2) and 25.73 ± 2.40 µg/cm(2)/h (TPE gel), respectively. Only plasmid from the PE and TPE could be found in the receiving solution with the cumulative amounts and fluxes at 6 h of 0.07 ± 0.01 µg/cm(2) and 0.40 ± 0.08 µg/cm(2)/h (PE solution); 0.10 ± 0.01 µg/cm(2) and 0.60 ± 0.06 µg/cm(2)/h (TPE solution); 0.88 ± 0.03 µg/cm(2) and 5.30 ± 0.15 µg/cm(2)/h (PE gel); and 1.02 ± 0.05 µg/cm(2) and 6.13 ± 0.28 µg/cm(2)/h (TPE gel), respectively. In stability studies, the plasmid still remained at 4 ± 2 °C and 25 ± 2 °C of about 48.00-65.20% and 27.40-51.10% (solution); and 12.34-38.31% and 8.63-36.10% (gel), respectively, whereas at 45 ± 2 °C, almost all the plasmid was degraded. These studies indicated the high potential application of Tat and an entrapment in elastic cationic niosomes for the development of transdermal gene delivery system.

摘要

描述了通过大鼠皮肤增强透皮吸收和稳定人酪氨酸酶质粒(P)的方法,使用 Tat(T)和包封在弹性阳离子脂质体(E)中。E(Tween61:胆固醇:DDAB 的摩尔比为 1:1:0.5)是通过使用 25%乙醇的冻干空脂质体(FDELs)方法制备的。TP 通过简单的混合方法制备。TPE 通过以 T:P:E 的比例 0.5:1:160 w/w/w 将 T 和 P 加载到 E 中制备。对于凝胶制剂,将 P、TP、PE 和 TPE 掺入 Carbopol 980 凝胶中(每 1g 凝胶中 30μg 质粒)。对于透皮吸收研究,从 TPE 的 0.31±0.04μg/cm(2)和 1.86±0.24μg/cm(2)/h(TPE 溶液);和 4.29±0.40μg/cm(2)和 25.73±2.40μg/cm(2)/h(TPE 凝胶),可以观察到活表皮和真皮(VED)中质粒的累积量和通量最高。只有来自 PE 和 TPE 的质粒可以在接收溶液中找到,在 6 小时时的累积量和通量为 0.07±0.01μg/cm(2)和 0.40±0.08μg/cm(2)/h(PE 溶液);0.10±0.01μg/cm(2)和 0.60±0.06μg/cm(2)/h(TPE 溶液);0.88±0.03μg/cm(2)和 5.30±0.15μg/cm(2)/h(PE 凝胶);和 1.02±0.05μg/cm(2)和 6.13±0.28μg/cm(2)/h(TPE 凝胶),分别。在稳定性研究中,质粒在 4±2°C 和 25±2°C 下仍保持约 48.00-65.20%和 27.40-51.10%(溶液);和 12.34-38.31%和 8.63-36.10%(凝胶),而在 45±2°C 时,几乎所有质粒都降解了。这些研究表明,Tat 和包封在弹性阳离子脂质体中的应用具有很大的潜力,可用于开发透皮基因传递系统。

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