Encapsulation of nanosuspensions in liposomes and microspheres

• US 20030096000A1
• Filed: 05/31/2002
• Published: 05/22/2003
• Est. Priority Date: 05/31/2001
• Status: Abandoned Application

• Current Assignee: Pacira Pharmaceuticals, Inc. (Pacira Biosciences, Inc.)
• Original Assignee: Pacira Pharmaceuticals, Inc. (Pacira Biosciences, Inc.)
• Inventors: Solis, Rosa Maria, Grenier, Pascal, Nhamias, Alain, Mantripragada, Sankaram
• Application Number:
  US10/161,969
• Publication Number:
  US 20030096000A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives

Abstract

Sustained release of hydrophobic agents may be achieved by incorporation of the agents into liposomes and microspheres. This is achieved by use of a nanosuspension comprising the hydrophobic agent. The nanosuspension may be used as the aqueous solution in the formation of the liposomes and microspheres.

Claims

1. A liposome comprising at least one hydrophobic agent dispersed in at least one chamber bounded by at least one membrane.

2. A liposome as in claim 1, wherein said at least one hydrophobic agent is a nanoparticle.

3. A liposome as in claim 2, wherein said nanoparticle is in a nanosuspension.

4. A liposome as in claim 2, wherein said nanoparticle has size ranging from about 1 nm to about 1 micron.

13. A liposome as in claim 1, wherein said at least one hydrophobic agent is further present in said at least one membrane.

15. A liposome as in claim 1, wherein said at least one membrane is formed by at least one lipid and at least one polymer in at least one bi-layer.

5. A multivesicular liposome comprising at least one hydrophobic agent dispersed in at least one chamber bounded by at least one membrane.

6. A multivesicular liposome as in claim 5, wherein said at least one hydrophobic agent is a nanoparticle.

7. A multivesicular liposome as in claim 6, wherein said nanoparticle is in a nanosuspension.

8. A multivesicular liposome as in claim 6, wherein said nanoparticle has size ranging from about 1 nm to about 1 micron.

14. A multivesicular liposome as in claim 5, wherein said at least one hydrophobic agent is further present in said at least one membrane.

16. A multivesicular liposome as in claim 5, wherein said at least one membrane is formed by at least one lipid and at least one polymer in at least one bi-layer.

17. A mutivesicular liposome as in claim 5, wherein multiple hydrophobic agents are present in the same of at least one chamber.

18. A multivesicular liposome as in claim 17, wherein at said multiple hydrophobic agents are nanoparticles.

19. A multivesicular liposome as in claim 18, wherein said nanoparticles are in at least one nosuspension.

20. A multivesicular liposome as in claim 18, wherein said nanoparticles have size ranging from about 1 nm to about 1 micron.

21. A multivesicular liposome as in claim 19, wherein said multiple hydrophobic agents are nanoparticles in a single nanosuspension.

22. A multivesicular liposome as in claim 21, wherein said nanoparticles have size ranging from about 1 nm to about 1 micron.

23. A mutivesicular liposome as in claim 5, wherein multiple hydrophobic agents are present in at least two different said chambers.

24. The multivesicular liposome as in claim 23, wherein said multiple hydrophobic agents are nanoparticles.

25. The multivesicular liposome as in claim 24, wherein said nanoparticles are in nanosuspensions.

26. The multivesicular liposome as in claim 24, wherein said nanoparticles have size ranging from about 1 nm to about 1 micron.

9. A microsphere comprising at least one hydrophobic agent dispersed in at least one internal chamber bounded by at least one membrane.

10. A microsphere as in claim 9, wherein said at least one hydrophobic agent is a nanoparticle.

11. A microsphere as in claim 10, wherein said nanoparticle is in a nanosuspension.

12. A microsphere as in claim 10, wherein said nanoparticle has size ranging from about 1 nm to about 1 micron.

27. A composition comprising at least one liposome comprising at least one hydrophobic agent dispersed in at least one chamber bounded by at least one membrane, and a pharmaceutically acceptable suspending agent.

28. A composition as in claim 27, wherein said at least one hydrophobic agent is a nanoparticle.

29. A composition as in claim 28, wherein said nanoparticle is in a nanosuspension.

30. A composition as in claim 28, wherein said at least one hydrophobic agent has size ranging from about 1 nm to about 1 micron.

31. A composition as in claim 28, wherein said at least one hydrophobic agent is perphenazine and said pharmaceutically acceptable suspending agent is substantially isotonic.

32. A composition comprising at least one multivesicular liposome comprising at least one hydrophobic agent dispersed in at least one chamber bounded by at least one membrane, and a pharmaceutically acceptable suspending agent.

33. A composition as in claim 32, wherein said at least one hydrophobic agent is a nanoparticle.

34. A composition as in claim 33, wherein said nanoparticle is in a nanosuspension.

35. A composition as in claim 33, wherein said at least one hydrophobic agent has size ranging from about 1 nm to about 1 micron.

36. A composition as in claim 33, wherein said at least one hydrophobic agent is perphenazine and said pharmaceutically acceptable suspending agent is substantially isotonic.

37. A composition comprising at least one microsphere comprising at least one hydrophobic agent dispersed in at least one internal chamber bounded by at least one membrane.

38. A composition as in claim 37, wherein said at least one hydrophobic agent is a nanoparticle.

39. A composition as in claim 38, wherein said nanoparticle is in a nanosuspension.

40. A composition as in claim 38, wherein said at least one hydrophobic agent has size ranging from about 1 nm to about 1 micron.

41. A composition as in claim 38, wherein said at least one hydrophobic agent is perphenazine and said pharmaceutically acceptable suspending agent is substantially isotonic.

42. A method for the sustained release of at least one hydrophic agent to a living being comprising administration to said living being of at least one liposome comprising the at least one hydrophic agent located within at least one liposome chamber.

43. A method as in claim 42, wherein said at least on hydrophobic agent is a nanoparticle.

44. A method as in claim 43, wherein said nanoparticle is in a nanosuspension.

45. A method as in claim 43, wherein said at least one hydrophobic agent has size ranging from about 1 nm to about 1 micron.

46. A method for the sustained release of at least one hydrophic agent to a living being comprising administration to said living being of at least one multivesicular liposome comprising the at least one hydrophic agent located within at least one multivesicular liposome chamber.

47. A method as in claim 46, wherein said at least on hydrophobic agent is a nanoparticle.

48. A method as in claim 47, wherein said nanoparticle is in a nanosuspension.

49. A method as in claim 47, wherein said at least one hydrophobic agent has size ranging from about 1 nm to about 1 micron.

50. A method for the sustained release of at least one hydrophic agent to a living being comprising administration to said living being of at least one microsphere comprising the at least one hydrophic agent located within at least one microsphere chamber.

51. A method as in claim 50, wherein said at least on hydrophobic agent is a nanoparticle.

52. A method as in claim 51, wherein said nanoparticle is in a nanosuspension.

53. A method as in claim 51, wherein said at least one hydrophobic agent has size ranging from about 1 nm to about 1 micron.

54. A method for preparing a liposome comprising the step of using a hydrophobic agent nanosuspension as the aqueous phase of the liposome.

55. A method of preparing a multivesicular liposome comprising the step of using at least one hydrophobic agent nanosuspension as the first aqueous phase of a double emulsion process.

56. The method as in claim 55 wherein at least two different said hydrophobic agent nanosuspensions are used sequentially as first aqueous phases, whereby each agent is encapsulated in separate chambers.

57. A method for preparing a microsphere comprising the step of using a hydrophobic agent nanosuspension as the aqueous phase of the microsphere.

58. In a method for preparing a liposome, wherein the improvement comprises use of at least one hydrophobic agent nanosuspension as the aqueous component of the liposome.

59. In a method for preparing a mutivesicular liposome, wherein the improvement comprises use of at least one hydrophobic agent nanosuspension as the first aqueous component of the multivesicular liposome.

60. In a method for preparing a microsphere, wherein the improvement comprises use of at least one hydrophobic agent nanosuspension as the aqueous component of the microsphere.

61. A liposome produced by the method comprising the step of using at least one nanosuspension as the aqueous phase of the liposome.

62. A microsphere produced by the method comprising the step of using at least one nanosuspension as the aqueous phase of the microsphere.

63. A method for delivering at least one hydrophobic agent to a living being comprising injecting said living being with a composition comprising at least one nanoparticle encapsulated in a liposome.

64. A method for delivering at least one hydrophobic agent to a living being comprising injecting said living being with a composition comprising at least one nanoparticle encapsulated in a multivesicular liposome.

65. A method for delivering at least one hydrophobic agent to a living being comprising injecting said living being with a composition comprising at least one nanoparticle encapsulated in a microsphere.

66. A method for delivering at least one hydrophobic agent to a living being comprising administration to said living being of at least one nanoparticle encapsulated in a liposome via an inhalation device selected from the group consisting of nebulizer, metered dose inhaler, spray bottle, and intratracheal tube.

67. A method for delivering at least one hydrophobic agent to a living being comprising administration to said living being of at least one nanoparticle encapsulated in a microsphere via an inhalation device selected from the group consisting of nebulizer, metered dose inhaler, spray bottle, and intratracheal tube.