Anionic-core composition for delivery of therapeutic agents, and methods of making and using the same

1. A composition comprising:

(a) a polymer consisting of

(i) a polymer backbone selected from polylysine, polyornithine, polyarginine, polyglutamate, polyaspartate, polycysteine, polyserine, polythreonine, polytyrosine, chondroitin sulfate, dermatan sulfate, keratan sulfate, carageenan, pectin, fucoidan, dextran, polymethylacrylic acid, polyacrylic acid, and polyallylamine;

(ii) multiple protective chains covalently linked to the polymer backbone, wherein each protective chain is independently selected from a group consisting of a linear poly(ethyleneglycol) and a linear methoxy poly(ethyleneglycol), and each protective chain is singly terminally covalently linked to a monomeric unit on the polymer backbone via one covalent bond;

(iii) an anionic group attached to a monomeric unit on the polymer backbone by a covalent bond, wherein the anionic group is selected from the group consisting of phosphate, sulfate, sulfonate, and carboxyl, or

an anionic cluster comprising two or more anionic groups attached to a monomeric unit on the polymer backbone by a single covalent bond, wherein the anionic groups are each selected from the group consisting of phosphate, sulfate, sulfonate, and carboxyl; and

(b) a load molecule linked directly by electrostatic interaction to the anionic group or the anionic cluster of the polymer without an intermediary metal ion, wherein the load molecule

(i) comprises a cell penetrating peptide;

(ii) comprises an anionic binding domain; or

(iii) has an isoelectric point greater than 7.3;

wherein at least 85% of the load molecule remains linked to the anionic group or the anionic cluster in the presence of 100 mM aqueous NaCl solution.

2. The composition of claim 1 , wherein the load molecule is selected from the group consisting of: (i) a peptide; (ii) a protein; and (iii) a small organic molecule.

3. The composition of claim 1 , wherein the load molecule is a peptide or a protein comprising a cell penetrating contiguous sequence of 5-10 amino acids, and wherein the number of basic amino acid (lysine and arginine) minus the number of acidic amino acids (glutamate and aspartate) is 2 or greater.

4. The composition of claim 3 , wherein the cell penetrating contiguous sequence in the peptide comprises of a sequence selected from the group consisting of: 1) Lys-Lys-Lys-Lys, 2) Lys-Lys-Lys-Arg, 3) Lys-Lys-Arg-Lys, 4) Lys-Lys-Arg-Arg, 4) Lys-Arg-Arg-Lys, 5) Lys-Arg-Arg-Arg, and 6) Arg-Arg-Arg-Arg, wherein any amino acid can be D or L isomer and the orientation of the sequence as presented can be amino to carboxyl or carboxyl to amino.

5. The composition of claim 1 , wherein the load molecule comprises an agent selected from the group consisting of SEQ ID NOS: 1-59, lysostaphin, an epithelial growth factor (EGF), an interferon, a Fibroblast growth factor (FGF), a Vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF), a Transforming growth factor (TGF), Nerve growth factor (NGF), and a Platelet derived growth factor (PDGF).

6. The composition of claim 1 , wherein the load molecule comprises an agent selected from the group consisting of the last 11 amino acids of SEQ ID NO: 1, the last 8 amino acids of SEQ ID NO: 5, the last 12 amino acids of SEQ ID NO: 7, the last 10 amino acids of SEQ ID NO: 9 and the last 14 amino acids of SEQ ID NO: 10.

7. The composition of claim 1 , wherein the load molecule comprises an anti-inflammatory agent selected from the group consisting of SEQ ID NOS: 1-11.

8. The composition of claim 1 , wherein the load molecule comprises an anti-infective agent selected from the group consisting of lysostaphin, interferon, and SEQ ID NOS: 12-45.

9. The composition of claim 1 , wherein the load molecule comprises a growth factor or an anti-apoptotic agent selected from the group consisting of SEQ ID NOS: 31-34 and 46-49 inclusive, a Fibroblast growth factor (FGF), a Vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF), a Transforming growth factor (TGF), Nerve growth factor (NGF), and a platelet derived growth factor (PDGF).

10. The composition of claim 1 , wherein the load molecule comprises a growth inhibitor selected from the group consisting of SEQ ID NOS: 50-59 and an interferon.

11. The composition of claim 1 , wherein the backbone is polylysine, and the anionic group is carboxyl.

12. The composition of claim 11 , wherein the load molecule is selected from the group consisting of SEQ ID NO: 26-29, 32-34, FGF, and HGF.

13. The composition of claim 1 , wherein the backbone is chondroitin.

14. The composition of claim 1 , wherein the load molecule is heparin binding EGF.

15. The composition of claim 1 , wherein the load molecule is lysostaphin.

16. The composition of claim 1 , wherein the load molecule is SEQ ID NO: 31.