THE USE OF TEMPERATURE TO CONTROL THE SIZE OF CATIONIC LIPOSOME/PLASMID DNA COMPLEXES

摘要

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