Stabilized polymeric carriers for therapeutic agent delivery
Polymeric carriers for the delivery of therapeutic agents and methods for making and using the same. The polymeric carriers include copolymers, diblock copolymers, polymeric architectures that include the copolymers and diblock copolymers, and particles assemblies comprising the copolymers, diblock copolymers, and polymeric architectures that include the copolymers.
1. A copolymer having the formula:
wherein
R 1 and R 2 are independently selected from hydrogen and methyl,
S is a poly(ethylene oxide) group,
X is O or NH,
D is a therapeutic agent,
C 1 is a cleavable linkage,
L 1 is a linker that covalently couples C 1 to X,
C 2 at each occurrence is an independent cleavable linkage,
L 2 is a linker that covalently couples C 1 to C 2 ,
n is 0 or 1,
a is an integer from about 5 to about 500,
b is an integer from about 5 to about 500, and
each * represents the copolymer terminus,
wherein C 1 and C 2 are independently selected from the group consisting of a phenyl ester, an acetal, a hemiacetal, a hemiacetal ester, a hydrazine, and an amino acid sequence cleavable by enzymatic action.
2. The copolymer of claim 1 , wherein L 1 is —(CH 2 ) n — where n is 2-10.
3. The copolymer claim 1 , wherein L 1 is —(CH 2 CH 2 O) n — where n is 2-4.
4. The copolymer of claim 1 , wherein L 2 is —(CH 2 ) n — where n is 2-10.
5. The copolymer of claim 1 , wherein L 2 is —(CH 2 CH 2 O) n — where n is 2-4.
6. The copolymer of claim 1 , wherein S is a poly(ethylene oxide) group having at least five ethylene oxide repeating units.
7. The copolymer of claim 1 , wherein S is a poly(ethylene oxide) group having from five (5) to thirty (30) ethylene oxide repeating units.
8. A method for administering a therapeutic agent to a subject, comprising administering a therapeutically effective amount of a copolymer of claim 1 to a subject in need thereof.
9. A method for treating a disease or condition treatable by a therapeutic agent, comprising administering a therapeutically effective amount of a copolymer of claim 1 to a subject in need thereof, wherein the therapeutic agent covalently coupled to the copolymer is effective to treat the disease or condition.
10. A copolymer having the formula:
wherein
R 1 and R 2 are independently selected from hydrogen and methyl,
S is a copolymer-stabilizing group,
X is O or NH,
D is a therapeutic agent,
C 1 is a cleavable linkage,
L 1 is a linker that covalently couples C 1 to X,
C 2 at each occurrence is an independent cleavable linkage,
L 2 is—a linker that covalently couples C 1 to C 2 —, wherein n1 is 2-10,
n is 1,
a is an integer from about 5 to about 500,
b is an integer from about 5 to about 500, and
each * represents the copolymer terminus,
wherein C 1 and C 2 are independently selected from the group consisting of a phenyl ester, an acetal, a hemiacetal, a hemiacetal ester, a hydrazine, and an amino acid sequence cleavable by enzymatic action.
11. The copolymer of claim 10 , wherein L 1 is —(CH 2 ) n — where n is 2-10.
12. The copolymer claim 10 , wherein L 1 is —(CH 2 CH 2 O) n — where n is 2-4.
13. The copolymer of claim 10 , wherein S comprises a poly(ethylene oxide) group.
14. The copolymer of claim 10 , wherein S comprises a poly(ethylene oxide) group having at least five ethylene oxide repeating units.
15. The copolymer of claim 10 , wherein S comprises a poly(ethylene oxide) group having from five (5) to thirty (30) ethylene oxide repeating units.
16. The copolymer of claim 10 , wherein S comprises a zwitterionic group.
17. The copolymer of claim 10 , wherein S comprises a zwitterionic group selected from the group consisting of a carboxybetaine group, a sulfobetaine group, and a phosphobetaine group.
18. A method for administering a therapeutic agent to a subject, comprising administering a therapeutically effective amount of a copolymer of claim 10 to a subject in need thereof.
19. A method for treating a disease or condition treatable by a therapeutic agent, comprising administering a therapeutically effective amount of a copolymer of claim 10 to a subject in need thereof, wherein the therapeutic agent covalently coupled to the copolymer is effective to treat the disease or condition.