Composite microneedle array including nanostructures thereon

• US 10,029,084 B2
• Filed: 12/19/2016
• Issued: 07/24/2018
• 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): STILES, AMBER R.
• Application Number:
  US15/382,774
• Publication Number:
  US 20170143949A1
• Time in Patent Office: 582 Days
• 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

Composite microneedle arrays including microneedles and a film overlaying the microneedles are provided. 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 film is adhered to the microneedle and at least partially conforms thereto, the film comprising a plurality of nanostructures that are arranged in a predetermined pattern on the second surface of the film to project outward from the second surface of the film, and wherein at least a portion of the nanostructures have a cross-sectional dimension of less than 500 nanometers and greater than 5 nanometers, a height of from 10 nanometers to 1 micrometer, and an aspect ratio of from 0.2 to 5.

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

3. The composite microneedle array according to claim 1, wherein at least a portion of the nanostructures have a cross-sectional dimension of less than 400 nanometers and greater than 10 nanometers.

4. The composite microneedle array according to claim 1, wherein the pattern further comprises microstructures, the nanostructures having a cross-sectional dimension smaller than the microstructures.

5. The composite microneedle array according to claim 4, 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 first nanostructures.

6. The composite microneedle array according to claim 1, wherein at least a portion of the nanostructures have a height of from 100 nanometers to 700 nanometers.

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

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

9. The composite microneedle array of claim 1, wherein the pattern has a fractal dimension of greater than 1 and less than 5.

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

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

12. 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 1:

1 and 1;

4.

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

14. The composite microneedle array of claim 1, wherein at least a portion of the nanostructures are in the form of pillars.

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

16. The composite microneedle array of claim 15, wherein the channel has a cross-sectional dimension of from 1 to 100 micrometers.

17. The composite microneedle array of claim 15, wherein the channel has a length of from 10 to 800 micrometers.

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

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

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

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

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

and 150°

.

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

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

25. The composite microneedle array of claim 24, wherein the polymer material includes a polyolefin, polystyrene, polycarbonate, polymethacrylate, polylactide, polyhydroxyalkanoate, or a combination thereof.

26. A transdermal patch comprising a composite microneedle 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 that are arranged in a predetermined pattern on the second surface of the film to project outward from the second surface of the film, and wherein at least a portion of the nanostructures have a cross-sectional dimension of less than 500 nanometers and greater than 5 nanometers, a height of from 10 nanometers to 1 micrometer, and an aspect ratio of from 0.2 to 5.

27. The transdermal patch according to claim 26, further comprising a reservoir for holding a drug compound.

28. The transdermal patch according to claim 27, further comprising a rate control membrane in fluid communication with the reservoir.

29. The transdermal patch according to claim 28, further comprising a release member that is generally impermeable to the drug compound and positioned adjacent to the rate control membrane.

30. The transdermal patch according to claim 27, wherein the drug compound has a molecular weight of greater than 100 kDa and less than 200 kDa.

31. The composite microneedle array of claim 26, wherein the nanostructures have a height of from 100 nanometers to 700 nanometers.

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

laying a film over a microneedle assembly, the microneedle assembly including a plurality of microneedles, 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, the nanostructures being arranged in a predetermined pattern to project outward from the second surface of the film, wherein at least a portion of the nanostructures have a cross-sectional dimension of less than 500 nanometers and greater than 5 nanometers, a height of from 10 nanometers to 1 micrometer and an aspect ratio of from 0.2 to 5; 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.

33. The method according to claim 32, further comprising forming the structures on the film.

34. The method according to claim 33, wherein the film and the nanostructures are fabricated simultaneously.

35. The method according to claim 33, wherein the structures are fabricated on the film according to a nanoimprint lithography process.

36. The method according to claim 32, 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.

37. The method according to claim 36, wherein the pressure is a vacuum pressure.

38. The method according to claim 36, wherein the pressure is applied to the second surface of the film.

39. The method according to claim 32, further comprising perforating the film at or near the microneedle tips.