High efficiency encapsulation of charged therapeutic agents...

A - Human Necessities – 61 – K

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A61K 9/00 (2006.01) A61K 9/127 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2289702

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 encapsula- tion efficiencies in excess of 50 %.

L'invention concerne des procédés de préparation d'une composition à base de lipides et d'acides nucléiques. Selon les procédés, on combine un mélange de lipides contenant un lipide protonable ou déprotonable, par exemple un lipide aminé et un lipide tel qu'un lipide modifié par PEG ou un oligomère polyamide, avec une solution aqueuse tamponnée d'un agent thérapeutique chargé, par exemple des acides nucléiques polyanioniques, afin de produire des particules dans lesquelles l'agent thérapeutique est encapsulé dans une vésicule lipidique. Les charges de surface sur les particules lipidiques sont neutralisées au moins partiellement afin de produire des compositions des agents thérapeutiques encapsulées par des lipides neutralisés en surface. Le procédé permet la préparation de compositions présentant des rapports élevés entre l'agent thérapeutique et le lipide et avec des efficacités d'encapsulation dépassant 50 %.

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