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用于基因转移的新型阳离子脂质制剂。

New cationic lipid formulations for gene transfer.

作者信息

Liu F, Yang J, Huang L, Liu D

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pennsylvania 15261, USA.

出版信息

Pharm Res. 1996 Dec;13(12):1856-60. doi: 10.1023/a:1016041326636.

Abstract

PURPOSE

To develop appropriate dosage forms of DNA for gene delivery.

METHODS

3 beta [N-(N', N' dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) was mixed either with Tween 80 alone, or with additional lipid components including castor oil and phosphatidylcholine (PC) or dioleoylphosphatidylethanolamine (DOPE) to make different lipid formulations. The particle size and the physical stability of the formulations upon mixing with plasmid DNA containing the luciferase cDNA were examined using laser light scattering measurement. The transfection activity of the DNA/lipid complexes was tested in presence or absence of serum using a cell culture system.

RESULTS

We demonstrated that many favorable properties as a gene carrier could be achieved by formulating DNA into new dosage forms using Tween 80 as the major emulsifier. Compared to the cationic liposomes, these new formulations transfected different cell lines with an equivalent or higher efficiency. Not only are they resistant to serum, but also form stable DNA complexes which could be stored for longer periods of time without losing transfection activity.

CONCLUSIONS

Cationic lipids formulated into different lipid formulations using Tween 80 as a surfactant appeared to have more favorable physical and biological activities than traditional cationic liposomes as a carrier for gene delivery.

摘要

目的

开发用于基因递送的合适DNA剂型。

方法

将3β-[N-(N',N'-二甲基氨基乙烷)氨基甲酰]胆固醇(DC-Chol)单独与吐温80混合,或与蓖麻油、磷脂酰胆碱(PC)或二油酰磷脂酰乙醇胺(DOPE)等其他脂质成分混合,制成不同的脂质制剂。使用激光散射测量法检测与含有荧光素酶cDNA的质粒DNA混合后制剂的粒径和物理稳定性。在有或无血清存在的情况下,使用细胞培养系统测试DNA/脂质复合物的转染活性。

结果

我们证明,以吐温80作为主要乳化剂将DNA制成新剂型可获得许多作为基因载体的良好特性。与阳离子脂质体相比,这些新制剂以同等或更高的效率转染不同的细胞系。它们不仅对血清有抗性,而且能形成稳定的DNA复合物,可长时间储存而不丧失转染活性。

结论

以吐温80作为表面活性剂制成不同脂质制剂的阳离子脂质作为基因递送载体,似乎比传统阳离子脂质体具有更良好的物理和生物学活性。

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