Polyamine modified particles

• US 20090110719A1
• Filed: 06/06/2005
• Published: 04/30/2009
• Est. Priority Date: 06/04/2004
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Kasturi, Sudhir Pai, Roy, Krishnendu
• Granted Patent: US 8,399,025 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 38/195 Chemokines, e.g. RANTES
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 48/0041 the non-active part being polymeric
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: C08J 2300/16 Biodegradable polymers
• CPC Class Codes: C08J 3/12 Powdering or granulating
• CPC Class Codes: C08L 2666/20 Macromolecular compounds having nitrogen in the main chain according to C08L75/00 - C08L79/00; Derivatives thereof
• CPC Class Codes: C08L 77/02 Polyamides derived from omega-amino carboxylic acids or from lactams thereof C08L77/10 takes precedence
• CPC Class Codes: C08L 77/06 Polyamides derived from polyamines and polycarboxylic acids C08L77/10 takes precedence

Abstract

A particle composition comprising a graft copolymer formed from a biocompatible polymer and a plurality of polyamine moieties, wherein the polyamine moieties are bound to the biocompatible polymer, and a combinatorial delivery polymer comprising a plurality of particles that comprises a graft copolymer formed from a biocompatible polymer and a plurality of polyamine moieties, wherein the polyamine moieties are bound to the biocompatible polymer, a plurality of nucleic acids electrostatically loaded onto the particles, a plurality of chemokine molecules, and a biodegradable polymer network, in which the loaded particles and chemokine molecules may be entrapped, are disclosed. Also disclosed is a method for treating a subject comprising administering a therapeutically effective dose of a pharmaceutical composition, the pharmaceutical composition comprising a particle composition that comprises a graft copolymer formed from a biocompatible polymer and a plurality of polyamine moieties, wherein the polyamine moieties are bound to the biocompatible polymer.

Claims

1. A particle composition comprising:

a graft copolymer formed from a biocompatible polymer and a plurality of polyamine moieties, wherein the polyamine moieties are bound to the biocompatible polymer.

2. The particle composition of claim 1, wherein the graft copolymer is biodegradable.

3. The particle composition of claim 1, further comprising at least one agent chosen from a therapeutic agent, a diagnostic agent, an imaging agent, a nucleic acid, a pDNA, an immunomodulatory agent, a cytokine, a chemokine, a chemo-attractant, an siRNA, a CpG oligonucleotide, a protein, and a peptide.

4. The particle composition of claim 1, further comprising a polymer network.

5. The particle composition of claim 1, wherein the plurality of polyamine moieties is capable of enhancing the transfection of the particle composition.

6. The particle composition of claim 1, wherein the plurality of polyamine moieties are covalently bound to the biocompatible polymer.

7. The particle composition of claim 1, wherein the plurality of polyamine moieties comprises at least one of moiety chosen from a polyethyleneimine, a polyhistidine, a carboxymethylcellulose, a putrescine, a spermidine, and a spermine.

8. The particle composition of claim 1, wherein the biocompatible polymer comprises at least one polymer chosen from a chitosan, a chitosan moiety, a poly(lactide-coglycolide), and a derivative thereof.

9. The particle composition of claim 1, further comprising at least one targeting ligand.

10. The particle composition of claim 1, further comprising at least one targeting ligand chosen from a sugar, a mannose, a fructose, a galactose, a protein, a monoclonal antibody, and a fragment thereof.

11. The particle composition of claim 1, wherein the biocompatible polymer comprises a chitosan moiety and the plurality of polyamine moieties comprises a plurality of polyethyleneimine moieties.

12. The particle composition of claim 1, wherein the biocompatible polymer comprises a chitosan moiety and the plurality of polyamine moieties comprises a plurality of polyethyleneimine moieties, and further comprising a nucleic acid.

13. The particle composition of claim 1, wherein the biocompatible polymer comprises a chitosan moiety and the plurality of polyamine moieties comprises a plurality of polyethyleneimine moieties, and further comprising carboxymethylcellulose.

14. The particle composition of claim 1, further comprising a particulate carrier system or a drug particle.

15. The particle composition of claim 1, further comprising a particulate carrier system or a drug particle, wherein the particulate carrier system or the drug particle comprises at least one structure chosen from a liposome, an emulsion, a microcapsule, a microsphere, and a nanoparticle.

36. The particle composition of claim 1, wherein the biocompatible polymer is poly(lactide-coglycolide) and wherein the plurality of polyamine moieties are provided by polyethyleneimine.

16-20. -20. (canceled)

21. A combinatorial delivery polymer comprising:

a plurality of particles that comprises a graft copolymer formed from a biocompatible polymer bound to and a plurality of polyamine moieties, wherein the polyamine moieties are bound to the biocompatible polymer;

a plurality of nucleic acids electrostatically loaded onto the particles;

a plurality of chemokine molecules; and

a biodegradable polymer network, in which the loaded particles and chemokine molecules may be entrapped.

22. The combinatorial delivery polymer of claim 21, wherein the particles comprise a graft copolymer formed from poly(lactide-coglycolide) bound to plurality of polyethyleneimine moieties.

23. The combinatorial delivery polymer of claim 21, wherein the nucleic acids comprise at least one molecule chosen from a pDNA and a CpG oligonucleotide.

24. The combinatorial delivery polymer of claim 21, wherein the plurality of chemokine molecules comprises at least one molecule chosen from MIP-3β

, MIP-3α

, a monocyte chemotactic protein, MCP-1, and MCP-3.

25. The combinatorial delivery polymer of claim 21, wherein the biodegradable polymer network is an in situ crosslinking, biodegradable, hydrogel network.

37. The combinatorial delivery polymer of claim 21, wherein the plurality of particles further comprise at least one agent chosen from a therapeutic agent, a diagnostic agent, an imaging agent, a nucleic acid, a pDNA, an immunomodulatory agent, a cytokine, a chemokine, a chemo-attractant, an siRNA, a CpG oligonucleotide, a protein, and a peptide.

38. The combinatorial delivery polymer of claim 21, wherein the plurality of polyamine moieties are covalently bound to the biocompatible polymer.

39. The combinatorial delivery polymer of claim 21, wherein the plurality of polyamine moieties comprises at least moiety chosen from a polyethyleneimine, a polyhistidien, a carboxymethylcellulose, a putrescine, a spermidine, and a spermine.

40. The combinatorial delivery polymer of claim 21, wherein the plurality of particles further comprise at least one targeting ligand.

41. The combinatorial delivery polymer of claim 21, wherein the plurality of particles further comprise at least one targeting ligand chosen from a sugar, a mannose, a fructose, a galactose, a protein, a monoclonal antibody, and a fragment thereof.

42. The combinatorial delivery polymer of claim 21, wherein the plurality of particles further comprise a particulate carrier system or a drug particle.

43. The combinatorial delivery polymer of claim 21, wherein the plurality of particles further comprise a particulate carrier system or a drug particle, and wherein the particulate carrier system or the drug particle comprises at least one structure chosen from a liposome, an emulsion, a microcapsule, a microsphere, and a nanoparticle.

26. A method for treating a subject comprising administering a therapeutically effective dose of a pharmaceutical composition, the pharmaceutical composition comprising a particle composition that comprises a graft copolymer formed from a biocompatible polymer and a plurality of polyamine moieties, wherein the polyamine moieties are bound to the biocompatible polymer.

27. The method of claim 26, further comprising at least one agent chosen from a therapeutic agent, a diagnostic agent, an imaging agent, a nucleic acid, a pDNA, an immunomodulatory molecule, a cytokine, a chemokine, a chemo-attractant, an siRNA, a CpG oligonucleotide, a protein, and a peptide.

28. The method of claim 26, wherein the pharmaceutical composition further comprises a polymer network.

29. The method of claim 26, wherein the plurality of polyamine moieties comprises at least one of moiety chosen from a polyethyleneimine, a polyhistidine, a carboxymethylcellulose, a putrescine, a spermidine, and a spermine

30. The method of claim 26, wherein the biocompatible polymer comprises at least one polymer chosen from a chitosan, a chitosan moiety, a poly(lactide-coglycolide), and a derivative thereof.

31. The method of claim 26, wherein the particle composition further comprises at least one targeting ligand.

32. The method of claim 26, wherein the particle composition further comprises At least one targeting ligand chosen from a sugar, a mannose, a fructose, a galactose, a protein, a monoclonal antibody, and a fragment thereof.

33. The method of claim 26, wherein the biocompatible polymer comprises a chitosan moiety and the plurality of polyamine moieties comprises a plurality of polyethyleneimine moieties.

34. The method of claim 26, wherein the pharmaceutical composition further comprises a particulate carrier system or a drug particle.

35. The method of claim 26, wherein the pharmaceutical composition further comprises a particulate carrier system or a drug particle, and wherein the particulate carrier system or a drug particle comprises at least one structure chosen from a liposome, an emulsion, a microcapsule, a microsphere, and a nanoparticle.