Tris(2-aminoethyl)amine-based 伪-branched fatty acid amides - Synthesis of lipids and comparative study of transfection efficiency of their lipid formulations

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• 作者：Nicole Erdmann^a ; Christian Wö ; lk^a ; ^b ; ^{christian.woelk@pharmazie.uni-halle.de" class="auth_mail" title="E-mail the corresponding author} ; Ingo Schulze^a ; Christopher Janich^a ; Manuela Folz^a ; Simon Drescher^c ; Matthias Dittrich^d ; Annette Meister^e ; Jü ; rgen Vogel^f ; Thomas Groth^f ; Bodo Dobner^a ; ^{bodo.dobner@pharmazie.uni-halle.de" class="auth_mail" title="E-mail the corresponding author} ; Andreas Langner^a
• 关键词：Cationic lipids ; Gene therapy ; Lipofection ; Lipoplex ; Non-viral gene transfer ; Synthetic methods
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：96
• 期：Complete
• 页码：349-362
• 全文大小：3182 K

文摘

The synthesis of a new class of cationic lipids, tris(2-aminoethyl)amine-based 伪-branched fatty acid amides, is described resulting in a series of lipids with specific variations in the lipophilic as well as the hydrophilic part of the lipids. In-vitro structure/transfection relationships were established by application of complexes of these lipids with plasmid DNA (pDNA) to different cell lines. The 伪-branched fatty acid amide bearing two tetradecyl chains and two lysine molecules (T14diLys) in mixture with the co-lipid 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphoethanolamine (DOPE) (1/2, n/n) exhibits effective pDNA transfer in three different cell lines, namely Hep-G2, A549, and COS-7. The presence of 10% serum during lipoplex incubation of the cells did not affect the transfection efficiency. Based on that, detailed investigations of the complexation of pDNA with the lipid formulation T14diLys/DOPE 1/2 (n/n) were carried out with respect to particle size and charge using dynamic light scattering (DLS), 味-potential measurements, and transmission electron microscopy (TEM). Additionally, the lipoplex uptake was investigated by confocal laser scanning microscopy (CLSM). Overall, lipoplexes prepared from T14diLys/DOPE 1/2 (n/n) offer large potential as lipid-based polynucleotide carriers and further justify advanced examinations.