Hydroxyl-modified cationic lipids with a carbamate linkage as gene delivery vehicles

Authors


Correspondence: Dr. Weihong Qiao, State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. China

E-mail: qiaoweihong2001@sina.com

Fax: 0086 0411 84986232

Abstract

We have developed four hydroxyl-modified cationic lipids with a carbamate linkage as delivery of DNA to the cervix cells. A formulation with cationic lipids and 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine at a molar ratio of 1:1, liposomes 1, 2, 3, and 4 were prepared by conventional thin film evaporation and ultrasonic method. Size and Zeta potential of liposome/DNA complexes were measured at different mass ratios, which were 1/1, 2/1, 3/1, 4/1, 6/1, and 8/1, respectively. Delivery of DNA to Hela cells by the liposomes was evaluated by measuring the transfection efficiency of liposome/DNA complexes. The cytotoxicity was investigated at the ratios above. Gene transfection efficiency of liposomes 1, 2, and 3-DNA complexes was approximately equal to that of Lipo2000–DNA complex, and a lower cytotoxicity compared with Lipo2000. The largest particle-size occurred at the break point from negative Zeta potential to positive Zeta potential. The biggest size of liposomes 1, 2, 3, and 4 was 1091, 760.5, 1584, and 436.5 nm, respectively. On head group, the length of carbon chain (lipo 2) could enhance transfection efficiency, while the hydroxy increase (lipo 3) could weaken a little. Moreover, the longer lipophilic tail (lipo 4) could evidently cut down the transfection efficiency.

Practical applications: The findings of the present study will be useful in biomedical applications for delivery of DNA to the cervix. Cationic lipid gene vectors in the condition of carbamate as connection bond and hydroxyalkyl group as head group may improve the gene therapy transfection efficiency and lower cytotoxicity. Research on high transfection efficiency and low toxic targeting gene vector will provide theoretical guidance and show practical significance for the development of promising gene delivery vehicles.

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