Fibers comprising polyesteramide copolymers for drug delivery
View Patent ↗The present inventioN relates to fibers comprising a polyesteramide (PEA) having a chemical formula described by structural formula (IV), wherein −m+p varies from 0.9-0.1 and q varies from 0.1 to 0.9, −m+p+q=1 whereby m or p could be 0, −n is about 5 to about 300; (pref. 50-200), —R 1 is independently selected from the group consisting of (C 2 -C 20 ) alkylene or (C 2 -C 20 ) alkenylene 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, —(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-; whereby a is at least 0.05 and b is at least 0.05 and a+b=1.
1. A fiber comprising a biodegradable poly(esteramide) copolymer (PEA) according to structural formula (IV),
wherein
m+p varies from 0.9-0.1 and q varies from 0.1 to 0.9
m+p+q=1 whereby m or p could be 0
n varies from 5 to 300;
—R 1 is independently selected from (C 2 -C 20 ) alkylene;
—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 6 -C 10 )aryl, —(CH 2 )SH, —(CH 2 ) 2 S(CH 3 ), —CH 2 OH, —CH(OH)CH 3 , —(CH 2 ) 4 NH 3 +, —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 —, HO-p-Ph-CH 2 —, (CH 3 ) 2 —CH—, Ph-NH—, NH—(CH 2 ) 3 —C—;
—R 5 is selected from the group consisting of (C 2 -C 20 )alkylene, alkyloxy, or oligoethyleneglycol;
—R 6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III), cycloalkyl fragments, aromatic fragments or heterocyclic fragments;
—R 7 is (C 6 -C 10 ) aryl (C 1 -C 6 )alkyl;
—R 8 is —(CH 2 ) 4 —;
wherein a is at least 0.05, b is at least 0.05 and a+b=1;
wherein the m unit and/or p unit, and the a and b units, are randomly distributed throughout the biodegradable poly(esteramide) copolymer, and
wherein the fibers have an average diameter of from 50 to 1000 μm.
2. The fiber according to claim 1 , wherein a is at least 0.5.
3. The fiber according to claim 1 , wherein a is at least 0.75.
4. The fiber according to claim 1 , wherein
p=0, m+q=1, m=0.75, a is 0.5, and a+b=1,
R 1 is —(CH 2 ) 8 —, R 3 is (CH 3 ) 2 —CH—CH 2 —, R 5 is hexyl, R 7 is benzyl, R 8 is —(CH 2 ) 4 —,
wherein the m, a, and b units are randomly distributed throughout the biodegradable poly(esteramide) copolymer.
5. The fiber according to claim 1 , wherein
m+p+q=1, q=0.25, p=0.45 and m=0.3, a is 0.5 and a+b=1;
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, R 7 is benzyl, R 8 is —(CH 2 ) 4 —;
R 6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III), and
wherein the m, p, a, and b units are randomly distributed throughout the biodegradable poly(esteramide) copolymer.
6. The fiber according to claim 1 , wherein
m+p+q=1, q=0.25, p=0.45 and m=0.3
a=0.75, a+b=1
R 1 is —(CH 2 ) 8 —; R 4 is (CH 3 ) 2 —CH—CH 2 —, R 7 is benzyl, R 8 is —(CH 2 ) 4 —;
R 6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III), and
wherein the m, p, a, and b units are randomly distributed throughout the biodegradable poly(esteramide) copolymer.
7. The fiber according to claim 1 , wherein
m+p+q=1, q=0.1, p=0.30 and m=0.6
a is 0.5 and a+b=1
R 1 —(CH 2 ) 4 —; R 3 and R 4 are (CH 3 ) 2 —CH—CH 2 —; R 7 benzyl, R 8 is —(CH 2 ) 4 —;
R 5 is (C 2 -C 20 )alkylene,
R 6 is selected from bicyclic-fragments of 1,4:3,6-dianhydrohexitols of structural formula (III), cycloalkyl fragments, aromatic fragments or heterocyclic fragments, and
wherein the m, p, a, and b units are randomly distributed throughout the biodegradable poly(esteramide) copolymer.
8. The fiber according to claim 1 , further comprising a bioactive agent.
9. A method for preparing a fiber according to claim 1 comprising the step of melt extruding a composition comprising the biodegradable poly(esteramide) copolymer.
10. A method for preparing a fiber according to claim 1 comprising the step of injection moulding a composition comprising the biodegradable copolymer.
11. The fiber according to claim 1 , wherein the fiber is degradable hydrolytically.
12. The fiber according to claim 1 , further comprising a bioactive agent dispersed in the biodegradable poly(esteramide) copolymer.
13. The fiber according to claim 12 , wherein the bioactive agent is incorporated into the fiber at an encapsulation efficiency of at least 20%.
14. The fiber according to claim 2 , further comprising a bioactive agent dispersed in the biodegradable poly(esteramide) copolymer.
15. The fiber according to claim 1 , further comprising a prostaglandin dispersed within the fiber.
16. The fiber according to claim 2 , further comprising a prostaglandin dispersed within the fiber.
17. The fiber according to claim 1 , further comprising a poly(ortho ester), poly(anhydride), poly(D,L-lactic acid), poly (L-lactic acid), poly(glycolic acid), copolymers of poly(lactic) and glycolic acid, poly(L-lactide), poly(D,L-lactide), poly(glycolide), poly(D,L-lactide-co-glycolide), or poly(L-lactide-co-glycolide), poly(phospho esters), poly(trimethylene carbonate), poly(oxa-esters), poly(oxa-amides), poly(ethylene carbonate), poly(propylene carbonate), poly(phosphoesters), poly(phosphazenes), poly(tyrosine derived carbonates), poly(tyrosine derived arylates), poly(tyrosine derived iminocarbonates), or combinations thereof.