Artificial low-density lipoprotein carriers for transport of substances across the blood-brain barrier
AssigneeBlanchette Rockefeller Neurosciences Institute
InventorsThomas Nelson, Alessandro Quattrone, Daniel Alkon
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Abstract
This invention relates to a highly efficient artificial low-density lipoprotein (LDL) carrier system for the targeted delivery therapeutic agents across the blood-brain barrier (BBB). In particular, this invention relates to artificial LDL particles comprised of three lipid elements: phosphatidyl choline, fatty-acyl-cholesterol esters, and at least one apolipoprotein. The present invention further relates to compositions, methods and kits comprising artificial LDL particles for targeting drugs to and across the BBB for the prevention and treatment of brain diseases.
Claims36
An artificial low-density lipoprotein (LDL) particle comprising artificial LDL, an outer phospholipid monolayer and a solid lipid core, wherein the outer phospholipid monolayer comprises at least one cloned apolipoprotein and the solid lipid core contains at least one therapeutic agent, wherein the at least one cloned apolipoprotein is apoliprotein E.
An artificial LDL particle for delivery of an agent across the blood-brain barrier comprising artificial LDL, an outer phosphatidylcholine monolayer, a solid lipid core comprising fatty acyl-cholesterol esters and a therapeutic agent, and cloned ApoE in the outer monolayer.
An artificial low-density lipoprotein (LDL) particle comprising an outer phospholipid monolayer comprising egg yolk phosphatidyl choline and cloned ApoE3, and a solid lipid core comprising cholesterol oleate and a therapeutic agent.
An artificial low low-density lipoprotein (LDL) particle produced by a method comprising the steps of:
- 1) suspending a mixture of phospholipids and lipids containing a therapeutic agent in a buffer solution;
- 2) sonicating the solution to form the outer phospholipid monolayer and solid lipid core;
- and 3) adding a solution comprising at least one cloned apolipoprotein, wherein the phospholipids and lipids are added in a ratio of between 11.5:1 to 12.5:1 by weight, and wherein the at least one apolipoprotein is ApoE incorporated into the outer phospholipid monolayer.
Dependencies are inferred from the claim text.