Composite microneedle array including nanostructures thereon

• US 9,526,883 B2
• Filed: 04/27/2011
• Issued: 12/27/2016
• Est. Priority Date: 04/28/2010
• Status: Active Grant

• Current Assignee: Sorrento Therapeutics Inc.
• Original Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Inventors: Ross, Russell Frederick
• Primary Examiner(s): Stigell, Theodore
• Assistant Examiner(s): STILES, AMBER R.
• Application Number:
  US13/641,504
• Publication Number:
  US 20130165861A1
• Time in Patent Office: 2,071 Days
• US Class Current: 1/1
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 38/191 Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0038 having a channel at the side surface
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: B29C 2059/023 Microembossing
• CPC Class Codes: B29C 59/002 Component parts, details or accessories; Auxiliary operations
• CPC Class Codes: B29C 59/026 of layered or coated substantially flat surfaces
• CPC Class Codes: B29K 2995/0056 Biocompatible, e.g. biopolymers or bioelastomers
• CPC Class Codes: B29L 2031/7544 Injection needles, syringes
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles
• CPC Class Codes: Y10T 156/10 Methods of surface bonding and/or assembly therefor
• CPC Class Codes: Y10T 156/1039 Surface deformation only of sandwich or lamina [e.g., embossed panels]
• CPC Class Codes: Y10T 156/1057 : Subsequent to assembly of laminae

Abstract

Disclosed are composite microneedles arrays including microneedles and a film overlaying the microneedles. The film includes a plurality of nano-sized structures fabricated thereon. Devices may be utilized for interacting with a component of the dermal connective tissue. A random or non-random pattern of structures may be fabricated such as a complex pattern including structures of differing sizes and/or shapes. Devices may be beneficially utilized for delivery of an agent to a cell or tissue. Devices may be utilized to directly or indirectly alter cell behavior through the interaction of a fabricated nanotopography with the plasma membrane of a cell and/or with an extracellular matrix component.

Claims

1. A composite microneedle array comprising

a microneedle assembly that includes a plurality of microneedles;

and

a film overlaying at least one microneedle of the microneedle assembly, the film having a first surface and a second surface, wherein the first surface of the is adhered to the microneedle and at least partially conforms thereto, the film comprising a plurality of nanostructures and microstructures that are arranged in a predetermined pattern and projecting directly outward from the second surface of the film, wherein at least a portion of the microstructures have a cross-sectional dimension of greater than about 500 nanometers and less than about 10 micrometers and a height of from about 20 nanometers to about 1 micrometer and wherein at least a portion of the nanostructures have a cross-sectional dimension of greater than about 5 nanometers and less than about 500 nanometers.

2. The composite microneedle array according to claim 1, at least one of the microneedles contains a channel along a length of the microneedle.

3. The composite microneedle array according to claim 1, further comprising second nanostructures having a cross-sectional dimension less than the cross-sectional dimension of the microstructures and greater than the cross-sectional dimension of the plurality of nanostructures.

4. The composite microneedle array according to claim 1, wherein at least a portion of the nanostructures have an aspect ratio of from about 0.2 to about 5.

5. The composite microneedle array of claim 1, wherein at least a portion of the nanostructures have a center-to-center spacing of from about 50 nanometers to about 1 micrometer.

6. The composite microneedle array of claim 1, wherein the pattern has a fractal dimension of greater than about 1.

7. The composite microneedle array of claim 1, wherein at least a portion of the nanostructures have a cross-sectional dimension of from about 100 to about 300 nanometers.

8. The composite microneedle array of claim 1, wherein the nanostructures have approximately the same cross-sectional dimension.

9. The composite microneedle array of claim 1, wherein the ratio of the cross sectional dimension of two adjacent nanostructures to the center-to-center spacing between those two structures is between about 1:

1 and about 1;

4.

10. The composite microneedle array of claim 1, wherein at least a portion of the nanostructures have an equidistant spacing.

11. The device according to claim 1, wherein at least a portion of the nanostructures are in the form of pillars.

12. The composite microneedle array of claim 1, wherein the microneedle contains a channel through which a drug compound is capable of flowing.

13. The composite microneedle array of claim 12, wherein the channel has a cross-sectional dimension of from about 1 to about 100 micrometers.

14. The composite microneedle array of claim 12, wherein the channel has a length of from about 10 to about 800 micrometers.

15. The composite microneedle array of claim 12, wherein the array contains a base having an aperture, wherein the aperture is in at least partial alignment with the channel of the microneedle.

16. The composite microneedle array of claim 1, wherein the microneedle has a length of from about 1 micrometer to about 1 millimeter.

17. The composite microneedle array of claim 1, wherein the nanostructures have a height of from about 10 nanometers to about 1 micrometer.

18. The composite microneedle array of claim 1, wherein the film exhibits an effective compression modulus between about 0.25 MPa and about 50 MPa.

19. The composite microneedle array of claim 1, wherein the film exhibits an effective shear modulus between about 4 MPa and about 320 MPa.

20. The composite microneedle array of claim 1, wherein the second surface of the film exhibits a water contact angle between about 80°

and about 150°

.

21. The composite microneedle array of claim 1, wherein the second surface of the film exhibits an average surface roughness between about 10 nanometers and about 200 nanometers.

22. The composite microneedle array of claim 1, wherein the film is formed from a polymeric material.

23. The composite microneedle array of claim 22, wherein the polymer material includes a polyolefin, polystyrene, polycarbonate, polymethacrylate, polylactide, polyhydroxyaikanoate, or a combination thereof.

24. The composite microneedle of claim 1, wherein at least a portion of the nanostructures have an aspect ratio of from about 0.5 to about 3.5.

25. The composite microneedle of claim 1, wherein at least a portion of the nanostructures have a cross-sectional dimension of from about 20 to about 400 nanometers and at least a portion of the microstructures have a cross-sectional dimension of from about 600 nanometers to about 1.5 micrometers.

26. The cornposite microneedle of claim 1, wherein at least a portion of the microstructures have an aspect ratio of from 0.2 to about 5.

27. The composite microneedle of claim 1, wherein the cross-sectional dimension of the microstructures is greater than the height of the microstructures.

28. The composite microneedle of claim 27, wherein at least a portion of the microstructures have an aspect ratio of from about 0.15 to 1.

29. The composite microneedle of claim 1, wherein at least a portion of the nanostructures have a height greater than a cross-sectional dimension.

30. A transdermal patch comprising a composite microneedie array, which comprises

a microneedle assembly that includes a plurality of microneedles;

and

a film overlaying at least one microneedle of the microneedle assembly, the film having a first surface and a second surface, wherein the first surface of the film is adhered to the microneedle and at least partially conforms thereto, the film comprising a plurality of nanostructures and microstructures that are arranged in a predetermined pattern and projecting directly outward from the second surface of the film, wherein at least a portion of the microstructures have a cross-sectional dimension of greater than about 500 nanometers and less than about 10 micrometers and a height of from about 20 nanometers to about 1 micrometer, and wherein at least a portion of the nanostructures have a cross-sectional dimension of greater than about 5 nanometers and less than about 500 nanometers.

31. The transdermal patch according to claim 30, further comprising a reservoir for holding a drug compound.

32. The transdermal patch according to claim 31, further comprising a rate control membrane in fluid communication with the reservoir.

33. The transdermal patch according to claim 32, further comprising a release member that is generally impermeable to the drug compound and positioned adjacent to the rate control membrane.

34. The transdermal patch according to claim 31, wherein the drug compound has a molecular weight of greater than about 100 kDa.

35. A method for forming a composite microneedle array comprising:

laying a film over a microneedle assembly, the microneedle assembly including a plurality of icroneedles, the film having a first surface and a second surface, the film at least partially conforming to the microneedles, wherein the first surface of the film contacts the microneedle assembly, the second surface of the film comprising a plurality of nanostructures and microstructures arranged in a predetermined pattern and projecting directly outward therefrom, wherein at least a portion of the microstructures have a cross-sectional dimension of greater than about 500 nanometers and less than about 10 micrometers and a height of from about 20 nanometers to about 1 micrometer, and wherein at least a portion of the nanostruotures have a cross-sectional dimension of greater than about 5 nanometers and less than about 500 nanometers; and

engaging the film with the microneedle assembly such that the film at least partially conforms to the microneedle array and adheres to the microneedle assembly.

36. The method according to claim 35, further comprising forming the structures on the film.

37. The method according to claim 36, wherein the film and the nanostructures are fabricated simultaneously.

38. The method according to claim 36, wherein the structures are fabricated on the film according to a nanoimprint lithography process.

39. The method according to claim 35, wherein the step of engaging the film with the microneedle assembly comprises the application of at least one of heat and pressure to the film.

40. The method according to claim 39, wherein the pressure is a vacuum pressure.

41. The method according to claim 39, wherein the pressure is applied to the second surface of the film.

42. The method according to claim 35, further comprising perforating the film at or near the microneedle tips.