Lipopolyplexes comprising imidazole/imidazolium lipophosphoramidate, histidinylated polyethyleneimine and siRNA as efficient formulation for siRNA transfection

Lipopolyplexes formulations resulting from association of nucleic acid, cationic liposomes and a cationic polymer are attracting formulations for siRNA delivery. Herein, imidazole- and imidazolium-based liposomes in association with histidinylated polymers are studied to produce siRNA lipopoplyplexe...

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Bibliographic Details
Published in:International journal of pharmaceutics 2014-01, Vol.460 (1-2), p.264-272
Main Authors: Gonçalves, Cristine, Berchel, Mathieu, Gosselin, Marie-Pierre, Malard, Virginie, Cheradame, Hervé, Jaffrès, Paul-Alain, Guégan, Philippe, Pichon, Chantal, Midoux, Patrick
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Green Fluorescent Proteins - genetics
HeLa Cells
Histidine
Histidine - chemistry
Humans
Imidazoles - chemistry
Life Sciences
Liposomes
Luciferases - genetics
Melanoma, Experimental
Polyethyleneimine - chemistry
Polymer
Polymers - chemistry
RNA
RNA interference
RNA, Messenger - metabolism
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - chemistry
Transfection
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Summary:Lipopolyplexes formulations resulting from association of nucleic acid, cationic liposomes and a cationic polymer are attracting formulations for siRNA delivery. Herein, imidazole- and imidazolium-based liposomes in association with histidinylated polymers are studied to produce siRNA lipopoplyplexes (LPRi) subsequently used for gene silencing. Several kinds of imidazole/histidine liposomes and cationic polymers are tested. The gene silencing effect is evaluated with synthetic siRNA directed against EGFP or luciferase mRNA, in HeLa cells stably expressing EGFP or B16F10 melanoma cells stably expressing luciferase, respectively. SiRNA formulations are compared with those prepared using some commercial transfection reagents. One formulation called His-lPEI LPRi100 comprising siRNA, histidinylated lPEI (His-lPEI) and liposomes 100 made with O,O-dioleyl-N-[3N-(N-methylimidazolium iodide)propylene] phosphoramidate and O,O-dioleyl-N-histamine phosphoramidate appears to give the best specific inhibition of gene expression at 10nM siRNA in a dose-dependent manner with low cytotoxicity. This formulation exhibits a size and a zeta potential of 60nm and +84mV, respectively. According to our previous works, histidinylated lipopolyplexes appears as a versatile formulation for DNA, mRNA and siRNA transfection.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2013.11.005