Subcutaneous delivery of poly(oxazoline) conjugates
The present disclosure provides polymer conjugates comprising a polymer and an agent, the agent linked to the polymer via a linking group containing a hydrolyzable moiety.
1. A polymer conjugate of the general formula (I),
wherein,
a is ran which indicates a random copolymer or block which indicates a block copolymer
o is an integer from 1 to 50;
m is an integer from 190 to 950;
p is 1-18;
R is hydrogen, alkyl or substituted alkyl; and
Ag is a dopamine agonist selected from the group consisting of: rotigotine, pramipexole, quinagolide, fenoldopam, apomorphine, 5-OH-DPAT, ropinirole, pergolide, cabergoline, and bromocriptine.
2. The polymer conjugate of claim 1 , wherein the dopamine agonist is rotigotine or (−)rotigotine.
3. The polymer conjugate of claim 1 , wherein the poly(oxazoline) polymer has a molecular weight range of 300 Da to 200,000 Da.
4. The polymer conjugate of claim 1 , wherein R is hydrogen.
5. The polymer conjugate of claim 1 , wherein R is alkyl.
6. The polymer conjugate of claim 1 wherein the polymer conjugate has structure:
7. The polymer conjugate of claim 1 , wherein the dopamine agonist is ropinirole.
8. The polymer conjugate of claim 1 , wherein the polymer conjugate has structure:
9. A method for treating a disease or condition related to dopamine insufficiency in the peripheral or central nervous system, the method comprising the step of administering to the subject an amount of a polymer conjugate, the polymer conjugate comprising a poly(oxazoline) polymer and an dopamine agonist, the dopamine agonist linked to the polymer by a releasable linker, the releasable linker cleavable in a subject and providing a sustained, controllable delivery of the dopamine agonist over a period of days to weeks.
10. The method of claim 9 , wherein the dopamine agonist is rotigotine or (−)rotigotine.
11. The method of claim 9 , wherein the dopamine agonist is ropinirole.
12. The method of claim 9 , wherein the polymer conjugate is administered alone or as a part of a pharmaceutical composition.
13. The method of claim 9 , wherein the polymer conjugate is administered in a therapeutically effective amount.
14. The method of claim 9 , wherein the polymer conjugate is administered by subcutaneous administration.
15. The method of claim 9 , wherein release of the dopamine agonist is controlled by the nature of the releasable linker, the size of the polymer, the method of delivery or a combination of the foregoing.
16. The method of claim 9 , wherein the polymer conjugate has the structure
wherein
R is hydrogen, alkyl or substituted alkyl;
p is 1 to 18;
a is ran which indicates a random copolymer or block which indicates a block copolymer;
o is an integer from 1 to 50; and
m is an integer from 190 to 950.
17. A method for treating Parkinson's disease, the method comprising the step of administering to the subject an amount of a polymer conjugate, wherein the polymer conjugate has the structure
wherein
R is hydrogen, alkyl or substituted alkyl;
p is 1 to 18;
a is ran which indicates a random copolymer or block which indicates a block copolymer;
o is an integer from 1 to 50; and
m is an integer from 190 to 950.