Polymeric Nanoparticles and Nanogels for Extraction and Release of Compounds

• US 20080260851A1
• Filed: 05/13/2005
• Published: 10/23/2008
• Est. Priority Date: 05/13/2004
• Status: Abandoned Application

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Somasundaran, Ponisseril, Chakraborty, Soma
• Application Number:
  US11/596,202
• Publication Number:
  US 20080260851A1
• Time in Patent Office: Days
• US Class Current: 424/501
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61L 9/042 with the help of a macromolecular compound as a carrier or diluent A61L9/048 takes precedence
• CPC Class Codes: A61L 9/048 air treating gels
• CPC Class Codes: B01J 13/0065 containing an organic phase
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C08F 2/22 Emulsion polymerisation
• CPC Class Codes: C08F 220/06 Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
• CPC Class Codes: C08F 251/02 on to cellulose or derivatives thereof
• CPC Class Codes: C08F 265/00 Macromolecular compounds obtained by polymerising monomers on to polymers of unsaturated monocarboxylic acids or derivatives thereof as defined in group C08F20/00
• CPC Class Codes: C08F 265/04 on to polymers of esters
• CPC Class Codes: C08F 265/10 on to polymers of amides or imides
• CPC Class Codes: C08F 2800/10 as molar percentages
• CPC Class Codes: C08F 2810/20 leading to a crosslinking, either explicitly or inherently
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C
• CPC Class Codes: C08F 8/32 by reaction with amines
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 51/003 grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds C08L51/04, C08L51/06 take precedence
• CPC Class Codes: C08L 51/02 grafted on to polysaccharides

Abstract

The invention relates to polymeric nanoparticles and nanogels, which can contain, deliver, and/or release one or more active agents, such as biologically active molecules or fragrance molecules, and methods of preparing the polymeric nanoparticles and nanogels. The nanoparticles are crosslinked utilizing radiation (g-radiation) as the catalyst for free radical polymerization (see FIG. 1) rather than by toxic chemical means. The nanoparticles and nanogels can be modified, without limitation, with hydrophobic, hydrophilic, or ionic groups or moieties. or with enzymes. Methods of preparing nanoparticles and nanogels containing or encapsulating a variety of molecules, including biologically active molecules and fragrance molecules, are provided.

Claims

1. A method of preparing polymeric nanoparticles, comprising:

(a) solubilizing one or more nonionic and ionic surfactants, or a combination thereof, in organic solvent;

(b) introducing at least one polymerizing reagent to the solution of step (a) to form a reaction mixture;

(c) purging oxygen from the reaction mixture of step (b);

(d) exposing the purged reaction mixture of step (c) to gamma (γ

) radiation for a time sufficient to crosslink nanoparticles formed in the reaction mixture; and

(e) precipitating the crosslinked nanoparticles from the reaction mixture.

2. The method according to claim 1, wherein the organic solvent comprises from 1-8 carbon atoms.

3. The method according to claim 2, wherein the organic solvent is hexane.

4. The method according to claim 1, wherein the at least one polymerizing reagent comprises one or more of acrylic acid and bisacrylamide monomers.

5. The method according to claim 1, wherein the surfactant is selected from sorbitan monooleate (SPAN 80®

), polyoxyethylene(20) sorbitan monooleate (TWEEN 80%) or sodium bis 2-ethylhexyl sulfosuccinate (AOT).

6. The method according to claim 5, wherein the surfactant is selected from sorbitan monooleate (SPAN 80®

) or polyoxyethylene(20) sorbitan monooleate (TWEEN 80®

).

7. The method according to claim 1, wherein the introducing step (b) further comprises a coupling or linking agent.

8. The method according to claim 7, wherein the coupling or linking agent is N-acryloxysuccinimide.

9. The method according to claim 1, wherein the purging step (c) comprises passing the reaction mixture through nitrogen gas.

10. The method according to claim 1, wherein the nanoparticles are precipitated with acetone.

11. The method according to claim 1, further comprising washing the nanoparticles with organic solvent following step (e).

12. The method according to claim 11, wherein the organic solvent is hexane.

13. The method according to claim 7, further comprising the step of modifying the nanoparticles with a functional group.

14. The method according to claim 13, wherein the nanoparticles are modified by incorporation of a functional group selected from one or more hydrophobic groups, hydrophilic groups, enzymes, ionic groups, or a combination thereof.

15. The method according to claim 14, wherein the functional group comprises one or more hydrophobic groups.

16. The method according to claim 15, wherein the functional group comprises one or more alkyl amine groups.

17. The method according to claim 16, wherein the one or more alkyl amine groups comprise propylamine or hexylamine.

18. The method according to claim 15, further comprising incorporating a fragrance molecule into the hydrophobically modified nanoparticles.

19. The method according to claim 18, wherein the fragrance molecule is linalyl acetate or vanillin.

20. A method of releasing a fragrance, comprising:

(a) hydrophobically modifying a polymeric nanoparticle;

(b) incorporating a fragrance molecule within the hydrophobically modified nanoparticle; and

(c) releasing the fragrance from the nanoparticle.

21. The method according to claim 20, wherein the releasing step (c) involves one or more of (i) changing the crosslinking density of the nanoparticle;

or (ii) changing the pH of the dispersion medium.

22. The method according to claim 20, further comprising the step of further modifying the nanoparticle with light sensitive molecules so that the fragrance is released upon exposure of the nanoparticle to light.

23. The method according to claim 22, wherein the light sensitive molecules are photolabile molecules.

24. The method according to claim 22, wherein the light is ultraviolet (UV) or non-UV light.

25. The method according to claim 20, further comprising co-polymerizing the hydrophobically modified nanoparticles with temperature-sensitive monomers to obtain temperature-sensitive nanoparticles comprising temperature-sensitive releasing properties of release of the fragrance.

26. The method according to claim 20, wherein the fragrance is linalyl acetate or vanillin.

27. The method according to claim 20, wherein in step (a) the nanoparticle is hydrophobically modified by the addition of N-acryloxysuccinimide to one or more polymerizing reagent monomers used to prepare modified nanoparticles.

28. The method according to claim 27, wherein the one or more polymerizing reagent monomers comprise acrylic acid and bisacrylamide monomers.

29. A method of releasing a biologically active molecule, comprising:

(a) hydrophobically modifying a polymeric nanoparticle;

(b) incorporating a biologically active molecule within the hydrophobically modified nanoparticle; and

(c) releasing the biologically active molecule from the nanoparticle.

30. The method according to claim 29, wherein the releasing step (c) involves one or more of (i) changing the crosslinking density of the nanoparticle;

or (ii) changing the pH of the dispersion medium.

31. The method according to claim 29, further comprising co-polymerizing the hydrophobically modified nanoparticles with temperature-sensitive monomers to obtain temperature-sensitive nanoparticles comprising temperature-sensitive properties of release of the biologically active molecule.

32. The method according to claim 29, further comprising the step of further modifying the nanoparticle with light sensitive molecules so that the fragrance is released upon exposure of the nanoparticle to light.

33. The method according to claim 32, wherein the light sensitive molecules are photolabile molecules.

34. The method according to claim 32, wherein the light is ultraviolet (UV) or non-UV light.

35. The method according to claim 29, wherein the biologically active molecule is selected from one or more of drugs, small molecules, antimicrobial agents, antibiotics, antitoxins, antibodies, pesticides, biocides, detoxifying agents, antifungal agents, enzymes, proteins, RNA molecules, antisense molecules, or a combination thereof.

36. The method according to claim 29, wherein in step (a) the nanoparticle is hydrophobically modified by the addition of N-acryloxysuccinimide to one or more polymerizing reagent monomers used to prepare the nanoparticles.

37. The method according to claim 36, wherein the one or more polymerizing reagent monomers comprise acrylic acid and bisacrylamide monomers.

56. The method according to claim 35 or claim 55, wherein the biologically active molecule is a drug.

57. The method according to claim 56, wherein the drug is bupivacaine or amitriptyline.

38. A method of preparing a functionally modified polymeric nanoparticle, comprising:

(a) solubilizing one or more nonionic and ionic surfactants, or a combination thereof, in organic solvent;

(b) introducing (i) at least one polymerizing monomer reagent and (ii) a linking reagent to the solution of step (a) to form a reaction mixture;

(c) purging oxygen from the reaction mixture of step (b);

(d) exposing the purged reaction mixture of step (c) to gamma (γ

) radiation for a time sufficient to crosslink nanoparticles formed in the reaction mixture;

(e) introducing a functional group or molecule into the reaction mixture; and

(f) precipitating the crosslinked and functionally modified nanoparticles from the reaction mixture.

39. The method according to claim 38, wherein the organic solvent comprises from 1-8 carbon atoms.

40. The method according to claim 38, wherein the organic solvent is hexane.

41. The method according to claim 38, wherein the at least one polymerizing monomer reagent comprises acrylic acid and bisacrylamide monomers.

42. The method according to claim 38, wherein the surfactant is selected from sorbitan monooleate (SPAN 80®

), polyoxyethylene(20) sorbitan monooleate (TWEEN 80®

) or sodium bis 2-ethylhexyl sulfosuccinate (AOT).

43. The method according to claim 42, wherein the surfactant is selected from sorbitan monooleate (SPAN 80®

) or polyoxyethylene(20) sorbitan monooleate (TWEEN 80®

).

44. The method according to claim 38, wherein the purging step (c) comprises passing the reaction mixture through nitrogen gas.

45. The method according to claim 38, wherein the nanoparticles are precipitated with acetone.

46. The method according to claim 38, further comprising washing the nanoparticles with organic solvent following step (d).

47. The method according to claim 46, wherein the organic solvent is hexane.

48. The method according to claim 38, wherein the nanoparticles are functionally modified by incorporation of a functional group or molecule selected from one or more hydrophobic groups or molecules, hydrophilic groups or molecules, enzymes, magnetic groups or molecules, or ionic groups or molecules.

49. The method according to claim 48, wherein the functional group or molecule comprises one or more hydrophobic groups.

50. The method according to claim 49, wherein the functional group comprises one or more alkylamine groups.

51. The method according to claim 50, wherein the one or more alkyl amine groups comprise propylamine or hexylamine.

52. The method according to claim 38, further comprising incorporating or encapsulating a fragrance molecule into the functionally modified nanoparticles.

53. The method according to claim 52, wherein the fragrance molecule is selected from linalyl acetate or vanillin.

54. The method according to claim 38, further comprising incorporating or encapsulating a biologically active molecule into the functionally modified nanoparticles.

55. The method according to claim 54, wherein the biologically active molecule is selected from one or more of drugs, small molecules, antimicrobial agents, antibiotics, antitoxins, antibodies, pesticides, biocides, detoxifying agents, antifungal agents, enzymes, proteins, RNA molecules, antisense molecules, or a combination thereof.

58. A method of preparing hydrophobically modified polymeric nanoparticles, comprising:

(a) solubilizing one or more nonionic and ionic surfactants, or a combination thereof, in organic solvent;

(b) introducing (i) at least one polymerizing monomer reagent and (ii) a linking reagent to the solution of step (a) to form a reaction mixture;

(c) purging oxygen from the reaction mixture of step (b);

(d) exposing the purged reaction mixture of step (c) to gamma (γ

) radiation for a time sufficient to crosslink nanoparticles formed in the reaction mixture;

(e) introducing a hydrophobic functional group or molecule into the reaction mixture; and

(f) precipitating the crosslinked and hydrophobically modified nanoparticles from the reaction mixture.

59. The method according to claim 58, wherein the organic solvent comprises from 1-8 carbon atoms.

60. The method according to claim 58, wherein the organic solvent is hexane.

61. The method according to claim 58, wherein the at least one polymerizing monomer reagent comprises acrylic acid and bisacrylamide monomers.

62. The method according to 58, wherein the surfactant is selected from sorbitan monooleate (SPAN 80®

), polyoxyethylene(20) sorbitan monooleate (TWEEN 80®

) or sodium bis 2-ethylhexyl sulfosuccinate (AOT).

63. The method according to claim 62, wherein the surfactant is selected from sorbitan monooleate (SPAN 80®

) or polyoxyethylene(20) sorbitan monooleate (TWEEN 80®

).

64. The method according to claim 58, wherein the purging step (c) comprises passing the reaction mixture through nitrogen gas.

65. The method according to claim 58, wherein the nanoparticles are precipitated with acetone.

66. The method according to claim 58, further comprising washing the nanoparticles with organic solvent following step (d).

67. The method according to claim 66, wherein the organic solvent is hexane.

68. The method according to claim 58, wherein the hydrophobic functional group or molecule comprises one or more alkylamine groups.

69. The method according to claim 68, wherein the one or more alkylamine groups comprise propylamine or hexylamine.

70. The method according to claim 58, further comprising incorporating or encapsulating a fragrance molecule into the hydrophobically modified nanoparticles.

71. The method according to claim 70, wherein the fragrance molecule is selected from linalyl acetate or vanillin.

72. The method according to claim 58, further comprising incorporating or encapsulating a biologically active molecule into the functionally modified nanoparticles.

73. The method according to claim 72, wherein the biologically active molecule is selected from one or more of drugs, small molecules, antimicrobial agents, antibiotics, antitoxins, antibodies, pesticides, biocides, detoxifying agents, antifungal agents, enzymes, proteins, RNA molecules, antisense molecules, or a combination thereof.

74. The method according to claim 73, wherein the biologically active molecule is a drug.

75. The method according to claim 74, wherein the drug is bupivacaine or amitriptyline.