Functionalized poly(ether-anhydride) block copolymers
The present application is directed to biodegradable polymers, compositions, including microspheres and nanospheres, formed of such polymers, and methods of using such polymers and compositions. In certain embodiments, the subject polymer compositions include therapeutic agents, optionally providing sustained release of the encapsulated agent after administration to a patient.
1. A block co-polymer, comprising:
(a) subunits of a diacid; and,
(b) a subunit of Formula B;
wherein:
Z is an end group that does not polymerize with the diacid; and,
n is, independently for each occurrence, an integer from 4-10,000.
2. The polymer of claim 1 , wherein the diacid subunits are of formula A:
m is, independently for each occurrence, an integer from 4 to 20; and,
p is, independently for each occurrence, an integer ≧1.
3. The polymer of claim 2 , wherein:
m is, independently for each occurrence, an integer from 4 to 12; and,
p is, independently for each occurrence, an integer from 5-10,000.
4. The polymer of claim 2 , wherein m is, independently for each occurrence, 8.
5. The polymer of claim 2 , wherein Z is Biotin-NH.
6. The polymer of claim 2 , wherein the subunits of Formula A comprise between 10% and 99% by weight of the polymer and the subunit of Formula B comprises between 1 and 90% by weight of the polymer.
7. The polymer of claim 6 , wherein the subunits of Formula A comprise between 15-98% by weight of the polymer and the subunit of Formula B comprises between 2-60% by weight of the polymer.
8. The polymer of claim 2 , having the formula:
9. The polymer of claim 8 , wherein the weight ratio of polysebacic acid to PEG-Biotin is selected from 95:5, 85:15, 75:25, and 50:50.
10. The polymer of claim 2 , further comprising:
(c) subunits of a diacid of Formula C:
wherein:
X is absent or, independently for each occurrence, represents a heteroatom selected from NR, O, and S;
q is, independently for each occurrence, an integer from 1 to 20; and,
r is, independently for each occurrence, an integer ≧1.
11. The polymer of claim 10 , wherein:
X is absent at each occurrence;
q is 3 or 6; and,
r is, independently for each occurrence, an integer from 5-10,000.
12. The polymer of claim 10 , wherein the subunits of Formula A comprise between 10-98% by weight of the polymer, the subunit of Formula B comprises between 1-80% by weight of the polymer, and the subunit of Formula C comprises between 1-95% by weight of the polymer.
13. A pharmaceutical composition, comprising: a polymer of claim 1 , wherein the polymer encapsulates an agent selected from: a therapeutic agent, a diagnostic agent, an imaging agent, and an adjuvant.
14. A pharmaceutical composition, comprising: a polymer of claim 1 .
15. The pharmaceutical composition of claim 14 , wherein the polymer is formulated as microspheres or nanospheres.
16. The pharmaceutical composition of claim 15 , wherein the polymer is formulated as microspheres.
17. The pharmaceutical composition of claim 16 , wherein the microspheres are suitable for administration by inhalation.
18. An inhaler, comprising: the microspheres of claim 16 .
19. A method for treating, preventing, or diagnosing a condition in a patient, comprising: administering to a patient in need thereof a composition of claim 14 .
20. The polymer of claim 1 , wherein the polymer has a M w of at least 10,000 daltons.
21. The polymer of claim 20 , wherein the polymer has a M w of at least 25,000 daltons.
22. A composition of claim 1 , wherein the subunits of Formula B have a molecular weight of at least 1,000 daltons.
23. A method for preparing a polymer of claim 2 , comprising:
(a) combining monomers of Formula A 1 and B 1 ; and,
(b) reacting the mixture at a temperature and time sufficient to form a polymer,
wherein:
R 1 is, independently for each occurrence, selected from H;
Y is, independently for each occurrence, selected from H and C 1-8 alkyl;
Z is a functional group that does not polymerize with the pre-polymer of Formula A;
m is, independently for each occurrence, an integer from 4 to 20;
n is, independently for each occurrence, an integer from 4 to 10,000; and,
p is, independently for each occurrence, an integer ≧1.
24. The method of claim 23 , wherein p is, independently for each occurrence, an integer from 5-10,000.
25. The method of claim 23 , wherein (a) further comprises: combining monomer of Formula C 1 with monomers of Formula A 1 and B 1 ;
wherein:
X is absent or, independently for each occurrence, is a heteroatom selected from NR, O, and S;
q is, independently for each occurrence, an integer from 1 to 20; and,
r is, independently for each occurrence, an integer ≧1.
26. The method of claim 25 , wherein q is, independently for each occurrence, an integer from 5-10,000.