Blood-stable, cholesterol-free liposomes
First Claim
1. A method of stabilizing freshly prepared, small, unilamellar liposomes in blood or body fluids, said liposomes consisting essentially of an unsaturated phosphatidylethanolamine and a fatty acid as the major components of the liposome preparation, which comprises adding a blood or body fluid stabilizing amount of a micelle-forming amphiphile to a suspension of said liposomes.
4 Assignments
0 Petitions
Accused Products
Abstract
Small unilamellar liposomes (d<600 nm) comprising an unsaturated phosphatidylethanolamine (PE) such as dioleoyl PE (DOPE) and a fatty acid such as oleic acid (OA) are stabilized by adding to a freshly prepared liposome suspension, an amphipile which has a high tendency to form micelles. Examples are shown for the following micelle-forming amphiphiles: lysophospholipide, gangliosides (GM1 and GTlb), sulfatide, synthetic glycopholipids such as sialo-lactosyl phosphatidylethanolamine, liopohilic drugs such as cytosine arabinoside diphosphate diacyglycerol, and proteins such as cytochrome b5, human high density lipoprotein (HDL), and human glycophorin A. The stabilized liposomes are resistant to the lytic action of albumin, the major blood component which causes the lysis of this type of liposome. Prior to the present invention, liposomes comprising PE and OA were typically stabilized by the incorporation of cholesterol.
-
Citations
22 Claims
- 1. A method of stabilizing freshly prepared, small, unilamellar liposomes in blood or body fluids, said liposomes consisting essentially of an unsaturated phosphatidylethanolamine and a fatty acid as the major components of the liposome preparation, which comprises adding a blood or body fluid stabilizing amount of a micelle-forming amphiphile to a suspension of said liposomes.
- 12. A method of stabilizing freshly prepared, small, unilamellar liposomes in blood or other body fluids, said liposomes consisting essentially of an unsaturated phosphatidylethanolamine and a fatty acid as the major components of the liposome preparation, which comprises mixing said liposomes with a stabilizing amount of human plasma, serum or whole blood.
-
21. A method of delivering one or more drugs to a mammalian patient so as to greatly reduce the chance of cross-contamination and cross-reaction of the blood of said patient with blood products from other sources, said method comprising the steps of:
-
(a) freshly preparing small unilamellar liposomes consisting essentially of (2;
1) DOPE;
OA, said liposomes encapsulating the one or more drugs to be delivered to said patient;(b) stabilizing the freshly prepared liposomes by mixing said liposomes with a stabilizing amount of the patient'"'"'s own blood, serum or plasma; and (c) injecting into the patient, an effective amount of the drug containing stabilized liposomes. - View Dependent Claims (22)
-
Specification