HIGH EFFICIENCY ENCAPSULATION OF CHARGED THERAPEUTIC AGENTS IN LIPID VESICLES

摘要

Methods for the preparation of a lipid-nucleic acidcomposition are provided. According to the methods, amixture of lipids containing a protonatable ordeprotonatable lipid, for example an amino lipid and a lipid such asa PEG- or polyamide oligomer-modified lipid is combinedwith a buffered aqueous solution of a charged therapeuticagent, for example polyanionic nucleic acids, to produceparticles in which the therapeutic agent is encapsulated ina lipid vesicle. Surface charges on the lipid particles areat least partially neutralized to provide surface-neutralizedlipid-encapsulated compositions of the therapeutic agents.The method permits the preparation of compositions withhigh ratios of therapeutic agent to lipid and with encapsula-tion efficiencies in excess of 50 %.