Brush amphiphilic block copolymers, and self-assembled nanoparticles therefrom

1. A brush amphiphilic block copolymer, comprising

a) at least one hydrophilic block comprising between 2 and 1000 monomeric units of:

wherein

R 1 is H or (C 1 -C 6 )-alkyl, optionally substituted with —COOR or —CON(R) 2 , wherein R is independently or simultaneously H or (C 1 -C 6 )-alkyl;

R 2 is H, (C 1 -C 20 )-alkyl, (C 2 -C 24 )-alkenyl, (C 2 -C 24 )-alkynyl, (C 6 -C 14 )-aryl, (C 5 -C 14 )-heteroaryl, or (C 1 -C 10 )-alkylene-(C 6 -C 14 )-aryl, wherein the latter 6 groups:

(i) are optionally substituted with halo, OH, or (C 1 -C 6 )-alkyl;

(ii) 1-3 carbon atoms are optionally replaced with O, NR′, or C(═O); and/or

(iii) optionally contain one or more functional groups comprising esters, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, disulfides, sulfone, sulfonate, phosphoesters, phosphoramidates, phosphazenes, a hydrophilic or hydrophobic polymer, heterocycles, or triazoles;

Z is O, NR′ or S;

R′ is H or (C 1 -C 6 )-alkyl; and

n is 0 or at least 2;

b) at least one hydrophobic block comprising between 2 and 1000 monomeric units of

wherein

R 3 is H or (C 1 -C 6 )-alkyl, optionally substituted with —COOR or —CON(R) 2 , wherein R is independently or simultaneously H or (C 1 -C 6 )-alkyl;

L is a linker;

Q is a hydrophobic polymer or copolymer; and

R 5 is H, (C 1 -C 20 )-alkyl, (C 2 -C 24 )-alkenyl, (C 2 -C 24 )-alkynyl, (C 6 -C 14 )-aryl, (C 5 -C 14 )-heteroaryl, or (C 1 -C 10 )-alkylene-(C 6 -C 14 )-aryl, wherein the latter 6 groups:

(i) are optionally substituted with halo, OH, or (C 1 -C 6 )-alkyl;

(ii) 1-3 carbon atoms are optionally replaced with O, NR′, or C(═O); and/or

(iii) optionally contain one or more functional groups comprising esters, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, sulfone, sulfonate, phosphoesters, phosphoramidates, phosphazenes, a hydrophilic or hydrophobic polymer, heterocycles or triazoles.

2. The brush amphiphilic block copolymer of claim 1 , wherein R 1 is H or (C 1 -C 3 )-alkyl, optionally substituted with —COOH.

3. The brush amphiphilic block copolymer of claim 1 , wherein R 2 is H, (C 1 -C 6 )-alkyl, (C 6 )-aryl, (C 5 -C 6 )-heteroaryl, or (C 1 -C 3 )-alkylene-(C 6 )-aryl, the latter four groups are

(i) are optionally substituted with (C 1 -C 3 )-alkyl;

(ii) 1-3 carbon atoms are optionally replaced with C(═O); and/or

(iii) optionally contain one or more functional groups comprising esters, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, disulfides, sulfone, sulfonate, phosphoesters, phosphoramidates, phosphazenes, a hydrophilic or hydrophobic polymer and/or a heterocycle.

4. The brush amphiphilic block copolymer of claim 1 , wherein n is an integer between 2 and 50.

5. The brush amphiphilic block copolymer of claim 1 , wherein the monomeric units of the hydrophilic block has the structure

wherein R 1 is H or (C 1 -C 6 )-alkyl.

6. The brush amphiphilic block copolymer of claim 1 , wherein the hydrophobic polymer or copolymer is a polyurethane, polythiourethane, polyether, polyamide, polyester, polyphosphazine, polyphosphamide, polyphosphodiester, polyureas, polythiourea, polyfumurates, or polyanhydride.

7. The brush amphiphilic block copolymer of claim 1 , wherein the linker L is (C 1 -C 20 )-alkyl, (C 2 -C 24 )-alkenyl, (C 2 -C 24 )-alkynyl, (C 6 -C 14 )-aryl, (C 5 -C 14 )-heteroaryl, or (C 1 -C 10 )-alkylene-(C 6 -C 14 )-aryl, wherein the latter 6 groups

(i) are optionally substituted with halo, OH, COOH, or (C 1 -C 6 )-alkyl;

(ii) 1-3 carbon atoms are optionally replaced with O, NR′, or C(═O); and/or

(iii) optionally contain one or more functional groups comprising esters, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, disulfides, sulfone, sulfonate, phosphoesters, phosphoramidates, phosphazenes, a hydrophilic or hydrophobic polymer, heterocycle or triazoles.

8. The brush amphiphilic block copolymer of claim 1 , wherein the at least one hydrophobic block comprises monomeric units of

wherein

R 3 is H or (C 1 -C 6 )-alkyl, optionally substituted with —COOR or —CON(R) 2 , wherein R is independently or simultaneously H or (C 1 -C 6 )-alkyl;

each R 4 is independently or simultaneously H, OH, COOH, (C 1 -C 10 )-alkyl, or aryl, wherein the latter two groups may optionally contain functional groups which are esters, acids, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, disulfides, sulfonamides, sulfones, sulfonates, phosphoesters, phosphoramidates, phosphazenes, a hydrophilic or hydrophobic polymer and/or a heterocycle;

R 5 is H, (C 1 -C 20 )-alkyl, (C 2 -C 24 )-alkenyl, (C 2 -C 24 )-alkynyl, (C 6 -C 14 )-aryl, (C 5 -C 14 )-heteroaryl, or (C 1 -C 10 )-alkylene-(C 6 -C 14 )-aryl, wherein the latter 6 groups:

(i) are optionally substituted with halo, OH, or (C 1 -C 6 )-alkyl;

(ii) 1-3 carbon atoms are optionally replaced with O, NR′, or C(═O); and/or

(iii) optionally contain one or more functional groups comprising esters, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, disulfides, sulfone, sulfonate, phosphoesters, phosphoramidates, phosphazenes, a hydrophilic or hydrophobic polymer and/or triazoles;

L is a linker;

X and Y are independently or simultaneously O, NR′ or S;

W is O or NR′;

R′ is H or (C 1 -C 6 )-alkyl;

each p is independently or simultaneously 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; and

m is at least 2.

9. The brush amphiphilic block copolymer of claim 1 , wherein R 3 is H or (C 1 -C 3 )-alkyl, optionally substituted with —COOH.

10. The brush amphiphilic block copolymer of claim 1 , wherein R 5 is H, (C 1 -C 6 )-alkyl, (C 6 )-aryl, (C 5 -C 6 )-heteroaryl, or (C 1 -C 3 )-alkylene-(C 6 )-aryl, the latter four groups are

(i) are optionally substituted with (C 1 -C 3 )-alkyl;

(ii) 1-3 carbon atoms are optionally replaced with C(═O); and/or

(iii) optionally contain one or more functional groups comprising esters, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, disulfides, sulfone, sulfonate, phosphoesters, phosphoramidates, phosphazenes, a hydrophilic or hydrophobic polymer and/or a heterocycle.

11. The brush amphiphilic block copolymer of claim 8 , wherein each R 4 is independently or simultaneously H, (C 1 -C 6 )-alkyl, or (C 6 -C 14 )-aryl, wherein the latter two groups may optionally contain esters, acids, thioesters, amides, ureas, thioureas, carbonates, carbamates, thiocarbamates, ethers, thioethers, primary, secondary, tertiary and/or quaternary amines, disulfides, sulfonamides, sulfones, sulfonates, phosphoesters, phosphoramidates, phosphazenes and/or a heterocycle.

12. The brush amphiphilic block copolymer of claim 8 , wherein p is 1, 2, 3, 4, 5, 6, 7 or 8.

13. The brush amphiphilic block copolymer of claim 1 , further comprising one or more additional monomers having the structure

wherein

R 6 is H or (C 1 -C 6 )-alkyl, optionally substituted with —COOR, wherein R is H or (C 1 -C 6 )-alkyl; and

K is a functional group which is —R″, —OR″, —SR″, —COOH, —COOR″, CON(R″) 2 , —S—S—R″, —R″OR″, —R″SR″, —R″COOR″, R″CON(R″) 2 , R″—S—S—R″, wherein R″ is (C 1 -C 10 )-alkenyl, (C 2 -C 10 )-alkynyl, (C 6 -C 10 )-aryl, (C 5 -C 10 )-heteroaryl, or (C 1 -C 10 )-alkylene-(C 6 -C 10 )-aryl.

14. The brush amphiphilic block copolymer of claim 13 , wherein R″ is (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 6 )-aryl, (C 5 -C 6 )-heteroaryl, or (C 1 -C 6 )-alkylene-(C 6 )-aryl.

15. A nanoparticle prepared via the self-assembly or directed assembly of the block copolymers as claimed in claim 1 .

16. The nanoparticle of claim 15 , wherein the nanoparticle is prepared by flash nanoprecipitation.

17. The nanoparticle of claim 15 , further comprising a drug or bioactive agent, wherein the drug or bioactive agent is encapsulated by the nanoparticle.

18. A method for the delivery of a drug or bioactive agent, comprising administering to a patient in need thereof, as nanoparticle as claimed in claim 17 .