Amphiphilic polymer-protein conjugates and methods of use thereof
View Patent ↗Compositions and methods for transporting biologically active proteins and polypeptides, particularly across the blood-brain barrier, are provided.
1. A method for delivering superoxide dismutase across the blood-brain barrier into the central nervous system of an animal comprising administering to said animal a composition comprising a conjugate comprising said superoxide dismutase conjugated to an amphiphilic block copolymer by anon-degradable linker moiety and at least one pharmaceutically acceptable carrier, wherein said amphiphilic block copolymer is a copolymer comprising at least one poly(oxyethylene) segment and at least one poly(oxypropylene) segment.
2. The method of claim 1 , wherein said amphiphilic block copolymer has a formula selected from the group consisting of:
wherein x, y, z, i, and j have values from about 2 to about 800; wherein in formulas (IV) and (V), for each R 1 and R 2 pair one is hydrogen and the other is a methyl group; wherein in formula (VI), R* is an alkylene of about 2 to about 6 carbons, a cycloalkylene of about 5 to about 8 carbons, or phenylene; R 1 and R 2 are either both represent hydrogen or one represents hydrogen and the other represents methyl; R 3 and R 4 are either both are hydrogen or one is hydrogen and the other is methyl; if both of R 3 and R 4 represent hydrogen, then one of R 5 and R 6 represents hydrogen and the other is methyl; if one of R 3 and R 4 represents methyl, then both R 5 and R 6 represent hydrogen; and A represents
3. The method of claim 2 , wherein said amphiphilic block copolymer is of the formula:
wherein x, y, and z have values from about 2 to about 800.
4. The method of claim 3 , wherein x, y, and z have values from about 5 to about 80.
5. The method of claim 1 , wherein said amphiphilic block copolymer has a hydrophilic-lipophilic balance (HLB) of less than or equal to 20.
6. The method of claim 5 , wherein said amphiphilic block copolymer has a hydrophilic-lipophilic balance (HLB) of less than or equal to 16.
7. The method of claim 6 , wherein said amphiphilic block copolymer has a hydrophilic-lipophilic balance (HLB) of less than or equal to 12.
8. The method of claim 6 , wherein said amphiphilic block copolymer has a hydrophilic-lipophilic balance (HLB) of less than or equal to 8.
9. The method of claim 1 , wherein the molecular weight of said poly(oxypropylene) segments of said amphiphilic block copolymer is from about 500 to about 5000.
10. The method of claim 9 , wherein the molecular weight of said poly(oxypropylene) segments of said amphiphilic block copolymer is from about 1600 to about 4000.
11. The method of claim 10 , wherein the molecular weight of said poly(oxypropylene) segments of said amphiphilic block copolymer is from about 2200 to about 3300.
12. The method of claim 1 , wherein said administration is intravenously.
13. A method for treating a neurodegenerative disease in a subject in need thereof, said method comprising administering to said subject a composition comprising:
a) a conjugate comprising superoxide dismutase conjugated to an amphiphilic block copolymer by a non-degradable linker moiety, and
b) at least one pharmaceutically acceptable carrier, wherein said amphiphilic block copolymer is a copolymer comprising at least one poly(oxyethylene) segment and at least one poly(oxypropylene) segment.
14. The method of claim 13 , wherein said administration is intravenously.