Bioactive components conjugated to substrates of microneedle arrays

• US 10,441,768 B2
• Filed: 03/18/2016
• Issued: 10/15/2019
• Est. Priority Date: 03/18/2015
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Falo, Jr., Louis D., Erdos, Geza
• Primary Examiner(s): Azpuru, Carlos A
• Application Number:
  US15/074,917
• Publication Number:
  US 20160271381A1
• Time in Patent Office: 1,306 Days
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2202/0007 introduced into the body
• CPC Class Codes: A61M 2202/0057 retained by adsorption
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B29C 39/025 for making multilayered articles
• CPC Class Codes: B29C 39/123 Making multilayered articles
• CPC Class Codes: B29C 41/22 Making multilayered or multicoloured articles
• CPC Class Codes: B29C 41/34 Component parts, details or accessories; Auxiliary operations
• CPC Class Codes: B29K 2001/08 Cellulose derivatives
• CPC Class Codes: B29K 2995/006 Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible
• CPC Class Codes: B29L 2031/753 Medical equipment; Accessories therefor bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008
• CPC Class Codes: B29L 2031/7544 Injection needles, syringes
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles

Abstract

Microneedle arrays and methods of forming the same can include one or more bioactive components bonded to a biocompatible material such that the one or more bioactive components are cleavable in vivo to release the bioactive component from the biocompatible material.

Claims

1. A dissolvable microneedle array for transdermal insertion into a patient comprising:

a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and

one or more bioactive components conjugated to the biocompatible material,

wherein the one or more bioactive components are cleavable in vivo by an enzyme to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material.

2. The microneedle array of claim 1, wherein the biocompatible material is carboxymethylcellulose.

3. The microneedle array of claim 1, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond.

4. The microneedle array of claim 1, wherein the one or more bioactive components are cleavable in vivo in response to pH, temperature, or both.

5. The microneedle array of claim 1, wherein the one or more bioactive components comprise Doxorubicin.

6. The microneedle array of claim 5, wherein the amount of Doxorubicin ranges from about 1 to 1000 μ

g for chemotherapy.

7. The microneedle array of claim 1, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion.

8. The microneedle array of claim 7, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material.

9. The microneedle array of claim 1, wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material.

10. The microneedle array of claim 9, wherein the at least two different bioactive components are selected from the group consisting of a chemotherapeutic agent, an adjuvant, and a chemo attractant for a cancer chemo immunotherapy application.

11. The microneedle array of claim 9, wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application.

12. The microneedle array of claim 1, wherein the one or more bioactive component comprises at least one viral vector.

13. The microneedle array of claim 12, wherein the at least one viral vector comprises an adenovector.

14. A dissolvable microneedle array for transdermal insertion into a patient comprising:

a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and

a first bioactive component conjugated to the biocompatible material, the bioactive component being Doxorubicin,

wherein the first bioactive component is cleavable in vivo by an enzyme to release the first bioactive component from the biocompatible material, or the first bioactive component retains function when conjugated to the biocompatible material.

15. The microneedle array of claim 14, wherein the biocompatible material is carboxymethylcellulose.

16. The microneedle array of claim 14, wherein the first bioactive component is bonded to the biocompatible material by a disulfide bond.

17. The microneedle array of claim 14, wherein the first bioactive components is cleavable in vivo in response to pH, temperature, or both.

18. The microneedle array of claim 14, wherein the amount of Doxorubicin ranges from about 1 to 1000 μ

g for chemotherapy.

19. The microneedle array of claim 14, further comprising a second bioactive component.

20. The microneedle array of claim 19, wherein the second bioactive component is selected from the group consisting of Poly-IC or Poly-ICLC.

21. The microneedle array of claim 19, wherein the second bioactive component is also conjugated to the biocompatible material.

22. The microneedle array of claim 19, wherein the second bioactive component is mixed into the biocompatible material.

23. A dissolvable microneedle array for transdermal insertion into a patient comprising:

a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and

one or more bioactive components conjugated to the biocompatible material,

wherein the one or more bioactive components are cleavable in vivo to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material, and

wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond which is cleavable in vivo by an enzyme.

24. The microneedle array of claim 23, wherein the one or more bioactive components are covalently bonded to the biocompatible material.

25. The microneedle array of claim 23, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond.

26. The microneedle array of claim 23, wherein the biocompatible material is carboxymethylcellulose.

27. The microneedle array of claim 23, wherein the one or more bioactive components comprise Doxorubicin.

28. The microneedle array of claim 27, wherein the amount of Doxorubicin ranges from about 1 to 1000 μ

g for chemotherapy.

29. The microneedle array of claim 23, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion.

30. The microneedle array of claim 29, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material.

31. The microneedle array of claim 23, wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material.

32. The microneedle array of claim 31, wherein the at least two different bioactive components are selected from the group consisting of a chemotherapeutic agent, an adjuvant, and a chemo attractant for a cancer chemo immunotherapy application.

33. The microneedle array of claim 31, wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application.

34. The microneedle array of claim 23, wherein the one or more bioactive component comprises at least one viral vector.

35. The microneedle array of claim 34, wherein the at least one viral vector comprises an adenovector.

36. A dissolvable microneedle array for transdermal insertion into a patient comprising:

a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and

one or more bioactive components conjugated to the biocompatible material,

wherein the one or more bioactive components are cleavable in vivo by an enzyme to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material, and

wherein the one or more bioactive component comprises at least one viral vector wherein the bioactive component is bonded to the biocompatible material by a disulfide bond which is cleavable in vivo by an enzyme.

37. The microneedle array of claim 36, wherein the one or more bioactive components are covalently bonded to the biocompatible material.

38. The microneedle array of claim 36, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond.

39. The microneedle array of claim 36, wherein the biocompatible material is carboxymethylcellulose.

40. The microneedle array of claim 36, wherein the one or more bioactive components are cleavable in vivo in response to pH, temperature, or both.

41. The microneedle array of claim 36, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion.

42. The microneedle array of claim 41, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material.

43. The microneedle array of claim 36, wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material.

44. The microneedle array of claim 43, wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application.

45. The microneedle array of claim 36, wherein the at least one viral vector comprises an adenovector.

46. A dissolvable microneedle array for transdermal insertion into a patient comprising:

a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and

one or more bioactive components conjugated to the biocompatible material,

wherein the one or more bioactive components are cleavable in vivo to release the bioactive component from the biocompatible material, or the bioactive component retains function when conjugated to the biocompatible material,

wherein the one or more bioactive components comprise at least two different bioactive components conjugated to the biocompatible material, and

wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application.

47. The microneedle array of claim 46, wherein the one or more bioactive components are covalently bonded to the biocompatible material.

48. The microneedle array of claim 46, wherein the one or more bioactive components are bonded to the biocompatible material by a disulfide bond.

49. The microneedle array of claim 46, wherein the biocompatible material is carboxymethylcellulose.

50. The microneedle array of claim 46, wherein the one or more bioactive components are cleavable in vivo by an enzyme.

51. The microneedle array of claim 46, wherein the one or more bioactive components are cleavable in vivo in response to pH, temperature, or both.

52. The microneedle array of claim 46, wherein the one or more bioactive components further comprise Doxorubicin.

53. The microneedle array of claim 52, wherein the amount of Doxorubicin ranges from about 1 to 1000 μ

g for chemotherapy.

54. The microneedle array of claim 46, wherein the one or more bioactive components are in a higher concentration in the plurality of microneedles than in the base portion.

55. The microneedle array of claim 54, wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein, the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array, and each microneedle comprises a plurality of layers of the biocompatible material.

56. The microneedle array of claim 46, wherein the one or more bioactive component further comprises at least one viral vector.

57. The microneedle array of claim 56, wherein the at least one viral vector comprises an adenovector.

58. A dissolvable microneedle array for transdermal insertion into a patient comprising:

a substrate comprising a biocompatible material that forms base portion and a plurality of microneedles extending from the base portion; and

a first bioactive component conjugated to the biocompatible material, the bioactive component being Doxorubicin,

wherein the first bioactive component is cleavable in vivo to release the first bioactive component from the biocompatible material, or the first bioactive component retains function when conjugated to the biocompatible material, and

wherein the second bioactive component is mixed into the biocompatible material wherein the bioactive components are bonded to the biocompatible material by a disulfide bond which is cleavable in vivo by an enzyme.

59. The microneedle array of claim 58, wherein the first bioactive component is covalently bonded to the biocompatible material.

60. The microneedle array of claim 58, wherein the first bioactive component is bonded to the biocompatible material by a disulfide bond.

61. The microneedle array of claim 58, wherein the biocompatible material is carboxymethylcellulose.

62. The microneedle array of claim 58, wherein the first bioactive components is cleavable in vivo in response to pH, temperature, or both.

63. The microneedle array of claim 58, wherein the amount of Doxorubicin ranges from about 1 to 1000 μ

g for chemotherapy.

64. The microneedle array of claim 58, wherein the second bioactive component is selected from the group consisting of Poly-IC or Poly-ICLC.