HIGH EFFICIENCY ENCAPSULATION OF CHARGED THERAPEUTIC AGENTS IN LIPID VESICLES
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Abstract
Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.
90 Citations
98 Claims
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1-83. -83. (canceled)
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84. A nucleic acid-lipid particle, said nucleic acid-lipid particle comprising:
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a nucleic acid; an amino lipid; a neutral lipid; a sterol; and a polyethyleneglycol-diacylglycerol (PEG-DAG) conjugate. - View Dependent Claims (85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98)
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Specification