Polyamine modified particles

• US 8,399,025 B2
• Filed: 06/06/2005
• Issued: 03/19/2013
• 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: Roy, Krishnendu, Kasturi, Sudhir Pai
• Primary Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US11/145,589
• Publication Number:
  US 20090110719A1
• Time in Patent Office: 2,843 Days
• Field of Search: 424/501, 424/489, 424/499, 514/951
• US Class Current: 424/501
• 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 of 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 poly(lactide-coglycolide) (PLGA) microparticle or nanoparticle comprising;

a plurality of PLGA polymers covalently surface functionalized by a plurality of polyethyleneimine (PEI) moieties in a graft copolymer.

2. 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.

3. The particle composition of claim 1, further comprising a biodegradable polymer network, in which the microparticle or nanoparticle may be entrapped.

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

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

6. 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.

16. The particle composition of claim 1, wherein the microparticle or nanoparticle has a Zeta potential of at least 1 mV at pH 7.4 in 1 mM HEPES buffer.

26. The particle composition of claim 1, wherein the PEI is attached to the PLGA via carbodiimide chemistry.

7. A combinatorial delivery polymer comprising:

a poly(lactide-coglycolide) (PLGA) microparticle or nanoparticle comprising a plurality of PLGA polymers covalently surface functionalized by a plurality of polyethyleneimine (PEI) moieties in a graft copolymer; and

a plurality of nucleic acids electrostatically bonded to the PEI moieties in the particles.

8. The combinatorial delivery polymer of claim 7, wherein the nucleic acids comprise at least one molecule chosen from an siRNA, a pDNA and a CpG oligonucleotide.

9. The combinatorial delivery polymer of claim 7, wherein the microparticle or nanoparticle further comprises at least one agent chosen from a therapeutic agent, a diagnostic agent, an imaging agent, an immunomodulatory agent, a cytokine, a chemo-attractant, a protein, and a peptide.

10. The combinatorial delivery polymer of claim 7, wherein the microparticle or nanoparticle further comprises at least one targeting ligand.

11. The combinatorial delivery polymer of claim 7, wherein the microparticle or nanoparticle 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.

12. The combinatorial delivery polymer of claim 7, further comprising a plurality of chemokine molecules.

13. The combinatorial delivery polymer of claim 7, further comprising a biodegradable polymer network, in which the microparticle or nanoparticle and a plurality of chemokine molecules may be entrapped.

14. The combinatorial delivery polymer of claim 12, 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.

15. The combinatorial delivery polymer of claim 13, wherein the biodegradable polymer network is an in situ crosslinking, biodegradable, hydrogel network.

17. The combinatorial delivery polymer of claim 7, wherein the microparticle or nanoparticle has a Zeta potential of at least 1 mV at pH 7.4 in 1 mM HEPES buffer.

27. The combinatorial delivery polymer of claim 7, wherein the PEI is attached to the PLGA via carbodiimide chemistry.

18. A particle composition comprising:

a poly(lactide-coglycolide) (PLGA) microparticle or nanoparticle comprising;

a plurality of PLGA polymers covalently bonded to the PEI moieties in a graft copolymer

wherein the microparticle or nanoparticle is operable to electrostatically bind a nucleic acid via the PEI moieties.

19. The particle composition of claim 18, 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.

20. The particle composition of claim 18, further comprising a polymer network.

21. The particle composition of claim 18, wherein the plurality of PEI moieties is capable of enhancing the transfection of the particle composition.

22. The particle composition of claim 18, further comprising at least one targeting ligand.

23. The particle composition of claim 18, 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.

24. The particle composition of claim 18, further comprising a particulate carrier system or a drug particle.

25. The particle composition of claim 18, wherein the microparticle or nanoparticle has a Zeta potential of at least 1 mV at pH 7.4 in 1 mM HEPES buffer.

28. The particle composition of claim 18, wherein the PEI is attached to the PLGA via carbodiimide chemistry.