Positively charged amphiphilic block copolymer as drug carrier and complex thereof with negatively charged drug

1. A block copolymer having the formula:

A-B-L-X-M  (1)

wherein X is —C(═O)—(CH 2 ) 2 —(C═O)—O—CH 2 CH 2 —Y or —C(═O)CHR 1 Y; wherein R 1 is H, a methyl, benzyl, 2-methylpropyl or 1-methylpropyl group; Y is —NH 3 + , —NRH 2 + , —NR 2 H + , or —NR 3 + wherein R is a methyl, ethyl or 2-hydroxyethyl group; and z denotes an integer from 0 to 6; M represents an anion; A is a biocompatible hydrophilic polymer; B is a biodegradable hydrophobic polymer; and L represents a linker selected from the group consisting of —O—, —NH—, —S— and —COO—.

2. The block copolymer of claim 1 wherein the number average molecular weight of each A and B is within the range of 100 to 100,000 Daltons.

3. The block copolymer of claim 1 wherein M is OH − , Cl − , Br − , I − , HSO 4 − , HCO 3 − or NO 3 − .

4. A block copolymer having the formula:

A 1 -B-L-X-M  (1b)

wherein X is —C(═O)—(CH 2 ) 2 —(C═O)—O—CH 2 CH 2 —Y or —C(═O)CHR 1 Y; wherein R 1 is H, a methyl, benzyl, 2-methylpropyl or 1- methylpropyl group, Y is —NH 3 + , —NRH 2 + , —NR 2 H + , or —NR 3 + wherein R is a methyl, ethyl or 2-hydroxyethyl group, and z denotes an integer from 0 to 6; M represents an anion; A 1 is a biocompatible hydrophilic polymer; B is a biodegradable hydrophobic polymer; L represents a linker selected from the group consisting of —O—, —NH—, —S— and —COO—; wherein said A 1 is a member selected from the group consisting of polyalkyleneglycol, polyalkyleneoxide, polyvinylpyrrolidone, polysaccharide, polyacrylamide, polymethacrylamide, polyvinylalcohol and derivatives thereof and said B is a biodegradable polyester.

5. The block copolymer of claim 4 wherein the number average molecular weight of each A 1 and B are within the range of 100 to 100,000 Daltons.

6. The block copolymer of claim 4 wherein M is OH − , Cl − , Br − , I − , HSO 4 − , HCO 3 − or NO 3 − .

7. A block copolymer having the formula:

A 2 -B 1 -L-X-M  (1c)

wherein X is —C(═O)—(CH 2 ) 2 —(C═O)—O—CH 2 CH 2 —Y or —C(═O)CHR 1 Y: wherein R 1 is H, a methyl, benzyl, 2-methylpropyl or 1- methylpropyl group, Y is —NH 3 + , —NRH 2 + , —NR 2 H + , or —NR 3 + wherein R is a methyl, ethyl or 2-hydroxyethyl group: and z denotes an integer from 0 to 6; M represents OH − an anion, A 2 is a biocompatible hydrophilic polymer; B 1 is a biodegradable hydrophobic polymer; L represents a linker selected from the group consisting of —O—, —NH—, —S— and —COO—; wherein said A 2 is a member selected from the group consisting of polyalkyleneglycol, polyalkyleneoxide, polyvinylpyrrolidone, polysaccharide, polyacrylamide, polymethacrylamide, polyvinylalcohol and derivatives thereof and said B 1 is a biodegradable polyester synthesized from monomers selected from the group consisting of D,L-lactide, D-lactide, L-lactide, D,L-lactic acid, D-lactic acid, L-lactic acid, glycolide, glycolic acid, ε-caprolactone, ε-hydroxy hexanoic acid and copolymers thereof.

8. The block copolymer of claim 7 wherein the number average molecular weight of both A 2 and B 1 are within the range of 100 to 100,000 Daltons.

9. The block copolymer of claim 7 wherein M is OH − , Cl − , Br − , I − , HSO 4 − , HCO 3 − or NO 3 − .

10. A block copolymer having the formula:

A 3 -B-L-X-M  (1d)

wherein X is —C(═O)—(CH 2 ) 2 —(C═O)—O—CH 2 CH 2 —Y or —C(═O)CHR 1 Y; wherein R 1 is H, a methyl, benzyl, 2-methylpropyl or 1- methylpropyl group, Y is —NH 3 + , —NRH 2 + , —NR 2 H + , or —NR 3 + wherein R is a methyl, ethyl or 2-hydroxyethyl group, and z denotes an integer from 0 to 6; M represents an anion; A 3 is a biocompatible hydrophilic polymer; B is a biodegradable hydrophobic polymer; L represents a linker selected from the group consisting of —O—, —NH—, —S— and —COO—; and wherein said A 3 is a degradable derivative prepared according to the following reaction scheme:

nZ+(n−1)Y′→Z-(Y′-Z) n−2 —Y′-Z

wherein Z represents a water-soluble polymer having a molecular weight of up to 5,000 Daltons, Y′ represents HOOC—(CH 2 ) m —COOH or O═C═N—(CH 2 ) m —N═C═O wherein m is an integer from 0 to 10 and n is an integer from 2 to 100.

11. The block copolymer of claim 10 wherein the number average molecular weight of both A 3 and B are within the range of 100 to 100,000 Daltons.

12. The block copolymer of claim 10 wherein M is OH − , Cl − , Br − , I − , HSO 4 − , HCO 3 − or NO 3 − .

13. A composition comprising the block copolymer of claim 1 and a negatively charged drug wherein said negatively charged drug combines with one or more of said block copolymers and forms a drug-block copolymer complex via electrostatic forces.

14. A composition comprising the block copolymer of claim 4 and a negatively charged drug wherein said negatively charged drug combines with one or more of said block copolymers and forms a drug-block copolymer complex via electrostatic forces.

15. A composition comprising the block copolymer of claim 7 and a negatively charged drug wherein said negatively charged drug combines with one or more of said block copolymers and forms a drug-block copolymer complex via electrostatic forces.

16. A composition comprising the block copolymer of claim 10 and a negatively charged drug wherein said negatively charged drug combines with one or more of said block copolymers and forms a drug-block copolymer complex via electrostatic forces.