LIPID CARRIER COMPOSITIONS WITH ENHANCED BLOOD STABILITY
Liposomes that contain at least 10 mol % of a negatively charged lipid coupled to a non-zwitterionic moiety are stable in the blood. Liposomes containing at least 1 mol % of such lipids may be frozen safely.
1 . A composition comprising liposomes wherein said liposomes comprise at least one vesicle forming lipid; at least 1 mol % of an aggregation preventing agent which is a negatively charged lipid comprising a non-zwitterionic moiety; and at least one biologically active agent and contain less than 20 mol % of cholesterol;
wherein said liposomes have a mean diameter between 80-200 nm+/−25 nm; and
wherein said liposomes have a transition temperature (T c ) of at least 38° C.
2 . The composition of claim 1 wherein said liposomes comprise a vesicle-forming lipid containing acyl groups of chain length of at least 18 carbon atoms.
3 . The composition of claim 1 wherein said aggregation preventing agent is a PEGylated amphipathic lipid or a phosphatidylglycerol (PG) or a phosphatidylinositol (PI).
4 . The composition of claim 3 wherein said aggregation preventing agent is a PG or a PI.
5 . The composition of claim 1 wherein said liposomes comprise at least 10 mol % of said aggregation preventing agent.
6 . The composition of claim 1 wherein said liposomes further contain a cryoprotectant.
7 . The composition of claim 1 which is cryostable.
8 . The composition of claim 1 in a frozen or lyophilized form.
9 . The composition of claim 1 wherein said liposome comprises 10 mol % of a PI or 10 mol % of a PG and wherein said vesicle forming lipid is distearoylphosphatidylcholine.
10 . The composition of claim 1 wherein said biologically active agent comprises FUDR and/or CPT11 and/or carboplatin.
11 . The composition of claim 1 which further contains a pharmaceutically acceptable excipient.
12 . A method to administer a biological agent to a subject in need of said agent which method comprises administering to said subject an effective amount of the composition of claim 1 .
13 . A method to preserve a liposome composition which comprises freezing or lyophilizing the composition of claim 1 .
14 . A method to preserve a liposome composition which comprises freezing or lyophilizing the composition of claim 6 .
15 . A method to preserve a liposome composition which comprises freezing or lyophilizing the composition of claim 7 .