Particles comprising polyesteramide copolymers for drug delivery

1. Microparticles with an average diameter of from 1 to 100 μm or nanoparticles with an average diameter of from 10 to less than 1000 nm comprising a bioactive agent and a biodegradable polyesteramide copolymer (PEA) according to the following formula:

wherein

m+p is from 0.9-0.1 and q is from 0.1 to 0.9;

m+p+q=1 whereby one of m or p could be 0;

n is about 5 to about 300;

a is at least 0.05, b is at least 0.05, a+b=1, qa=q*a, and qb=q*b; wherein units of m (if present), units of p (if present), units of qa, and units of qb are all randomly distributed throughout the copolymer;

R 1 is independently selected from the group consisting of (C 2 -C 20 ) alkylene, (C 2 -C 20 ) alkenylene, —(R 9 —CO—O—R 10 —O—CO—R 9 )—, —CHR 11 —O—CO—R 12 —COOCR 11 —, and combinations thereof;

R 3 and R 4 in a single backbone unit m or p, respectively, are independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 6 -C 10 )aryl, (C 1 -C 6 )alkyl, —(CH 2 )SH, —(CH 2 ) 2 S(CH 3 ), —CH 2 OH, —CH(OH)CH 3 , —(CH 2 ) 4 NH 3 +, —(CH 2 ) 3 NHC(═NH 2 +)NH 2 , —CH 2 COOH, —(CH 2 )COOH, —CH 2 —CO—NH 2 , —CH 2 CH 2 —CO—NH 2 , —CH 2 CH 2 COOH, CH 3 —CH 2 —CH(CH 3 )—, (CH 3 ) 2 —CH—CH 2 —, H 2 N—(CH 2 ) 4 —, Ph-CH 2 —, CH═C—CH 2 —, HO-p-Ph-CH 2 —, (CH 3 ) 2 —CH—, Ph-NH—, NH—(CH 2 ) 3 —C—, NH—CH═N—CH═C—CH 2 —;

R 5 is selected from the group consisting of (C 2 -C 20 )alkylene, (C 2 -C 20 )alkenylene, alkyloxy or oligoethyleneglycol;

R 6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III);

R 7 is selected from the group consisting of (C 6 -C 10 ) aryl (C 1 -C 6 )alkyl;

R 8 is —(CH 2 ) 4 —;

R 9 or R 10 are independently selected from C 2 -C 12 alkylene or C 2 -C 12 alkenylene;

R 11 or R 12 are independently selected from H, methyl, C 2 -C 12 alkylene or C 2 -C 12 alkenylene.

2. The microparticles or nanoparticles according to claim 1 , wherein a is at least 0.5.

3. The microparticles or nanoparticles according to claim 1 , wherein a is at least 0.75.

4. The microparticles or nanoparticles according to claim 1 , wherein

p=0, m=0.75, and a=0.5;

wherein the m, qa, and qb units are randomly distributed;

R 1 is —(CH 2 ) 8 —, R 3 is (CH 3 ) 2 —CH—CH 2 —, R 5 is hexyl, and R 7 is benzyl.

5. The microparticles or nanoparticles according to claim 1 , wherein

m=0.3, p=0.45, q=0.25, and a=0.5;

wherein the m, p, qa, and qb units are randomly distributed;

R 1 is —(CH 2 ) 8 —; R 3 and R 4 respectively, are (CH 3 ) 2 —CH—CH 2 —; R 5 is (C 2 -C 20 )alkylene; and R 7 is benzyl.

6. The microparticles or nanoparticles according to claim 1 , wherein

m=0.3, p=0.45, q=0.25, and a=0.75;

wherein the m, p, qa, and qb units are randomly distributed;

R 1 is —(CH 2 ) 8 —; R 4 is (CH 3 ) 2 —CH—CH 2 —; and R 7 is benzyl.

7. The microparticles or nanoparticles according to claim 1 , wherein

m=0.6, p=0.30, q=0.1, and a=0.5;

wherein the m, p, qa, and qb units are randomly distributed;

R 1 —(CH 2 ) 4 —; R 3 and R 4 respectively, are (CH 3 ) 2 —CH—CH 2 —; and R 7 benzyl.

8. The microparticles or nanoparticles according to claim 1 , wherein R 1 is independently selected from (C 2 -C 20 )alkylene.

9. The microparticles or nanoparticles according to claim 1 , wherein R 5 is (C 2 -C 20 )alkylene.

10. The microparticles or nanoparticles according to claim 8 , wherein R 5 is (C 2 -C 20 )alkylene.

11. The microparticles or nanoparticles according to claim 1 , wherein the bioactive agent is a small molecule drug, or prodrug or metabolite thereof.

12. The microparticles or nanoparticles according to claim 5 , wherein the bioactive agent is a small molecule drug, or prodrug or metabolite thereof.

13. The microparticles or nanoparticles according to claim 10 , wherein the bioactive agent is a small molecule drug, or prodrug or metabolite thereof.

14. The microparticles or nanoparticles according to claim 1 , comprising an inner core and an outer shell structure.

15. A composition comprising the microparticles or nanoparticles according to claim 11 .

16. A composition comprising the microparticles or nanoparticles according to claim 12 .

17. A composition comprising the microparticles or nanoparticles according to claim 13 .

18. An article or device comprising the microparticles or nanoparticles according to claim 11 .

19. An article or device comprising the microparticles or nanoparticles according to claim 12 .

20. An article or device comprising the microparticles or nanoparticles according to claim 13 .