The use of temperature to control the size of cationic...

A - Human Necessities – 61 – K

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A61K 9/127 (2006.01) A61K 48/00 (2006.01) C12N 15/88 (2006.01)

Patent

CA 2284193

Methods of forming cationic liposome/nucleic acid complexes in which the complexes have a mean diameter of about 200 to about 300 nm are provided. The complexes are formed by combining a first solution of preformed cationic unilamellar liposomes with a mean diameter of from 100 to 150 nm, with a second solution of nucleic acid. Each of the solutions are equilibrated prior to mixing to temperatures of from 0 ~C to about 12 ~C, preferably about 2 ~C to about 7 ~C. The preformed cationic liposomes are typically prepared from an unsaturated cationic lipid, for example DODAC, DOTAP, DOTMA, DODAP, DMRIE, DORI, DOSPA and combinations thereof, and a neutral lipid, for example DOPE or cholesterol. The combination of the first and second solutions is typically carried out by gentle mixing over ice for a period of time of from about 10 to about 60 minutes.

Procédés de formation de complexes d'acide nucléique/liposomes cationiques, ayant un diamètre moyen d'environ 200 à 300 nm. On forme lesdits complexes en combinant une première solution de liposomes monolamellaires cationiques préformés ayant un diamètre moyen d'environ 10 à 150 nm, avec une deuxième solution d'acide nucléique. Chaque solution est équilibrée avant d'être mélangée, à des températures de 0 ·C à environ 12 ·C, de préférence d'environ 2 ·C à 7 ·C. On prépare généralement les liposomes cationiques préformés à partir d'un lipide cationique insaturé, tel que DODAC, DOTAP, DOTMA, DODAP, DMRIE, DORI, DOSPA, et des combinaisons de ceux-ci, et d'un lipide neutre, tel que DOPE ou le cholestérol. Pour combiner les première et deuxième solutions, on les mélange généralement délicatement au-dessus de la glace pendant environ 10 à 60 minutes.

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