Nanopatterned medical device with enhanced cellular interaction

• US 10,245,421 B2
• Filed: 04/27/2011
• Issued: 04/02/2019
• Est. Priority Date: 04/28/2010
• Status: Active Grant

• Current Assignee: Sorrento Therapeutics Inc.
• Original Assignee: Sorrento Therapeutics Inc.
• Inventors: Ross, Russell Frederick
• Primary Examiner(s): Price, Nathan R
• Assistant Examiner(s): Bui, Anh
• Application Number:
  US13/095,489
• Publication Number:
  US 20110270221A1
• Time in Patent Office: 2,897 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

Disclosed are nanotopography-based methods and devices for interacting with a component of the dermal connective tissue. Devices include structures fabricated on a surface to form a nanotopography. A random or non-random pattern of structures may be fabricated such as a complex pattern including structures of differing sizes and/or shapes. Microneedles 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 medical device for delivering a drug compound through a stratum corneum and to a subdermal location, the device comprising:

a support having an aperture;

an array of microneedles that extend outwardly from the support, wherein at least one microneedle contains a shaft that has an outer wall extending from the support to a tip, wherein the tip and at least a portion of the outer wall are configured to penetrate the stratum corneum, wherein a plurality of nanostructures are spaced about an external surface of the outer wall in a predetermined pattern, and wherein at least a portion of the nanostructures have a cross-sectional dimension of less than about 500 nanometers and greater than about 5 nanometers and an aspect ratio of from about 0.2 to about 5, wherein the microneedle contains a channel in a side of the microneedle, wherein the aperture is in at least partial alignment with the channel of the microneedle, wherein at least a portion of the microneedles has a cross-sectional dimension of from about 1 micrometer to about 1 millimeter; and

a reservoir wherein the drug compound is retained, the reservoir being in fluid communication with the channel of the microneedle for delivery to the subdermal location.

2. The medical device of claim 1, wherein at least a portion of the nanostructures have a cross-sectional dimension of less than about 300 nanometers, and greater than about 100 nanometers.

3. The medical device of claim 1, wherein the nanostructures have approximately the same cross-sectional dimension.

4. The medical device of claim 1, wherein the pattern further includes microstructures, wherein the nanostructures have a cross-sectional dimension smaller than the microstructures.

5. The medical device of claim 4, wherein the microstructures have a cross-sectional dimension of greater than about 500 nanometers and less than about 10 micrometers and the nanostructures have a cross-sectional dimension of less than about 300 nanometers.

6. The medical device of 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 plurality of nanostructures.

7. The medical device 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.

8. The medical device of claim 1, wherein the ratio of the cross-sectional dimension of two adjacent nanostructures to a center-to-center spacing between those two structures is between about 1:

1 and about 1;

4.

9. The medical device of claim 1, wherein at least a portion of the nanostructures have an equidistant spacing.

10. The medical device of claim 1, wherein at least a portion of the nanostructures have a height of from about 100 nanometers to about 700 nanometers.

11. The medical device of claim 1, wherein the pattern has a fractal dimension of greater than about 1.

12. The medical device of claim 1, wherein the pattern has a fractal dimension of from about 1.5 to about 2.5.

13. The medical device of claim 1, wherein the external surface has an average surface roughness between about 10 nanometers and about 200 nanometers.

14. The medical device of claim 1, wherein the external surface has an effective shear modulus between about 4 MPa and about 320 MPa.

15. The medical device of claim 1, wherein the external surface has an effective compression modulus between about 0.2 MPa and about 50 MPa.

16. The medical device of claim 1, wherein the external surface has a water contact angle between about 80°

and about 150°

.

17. The medical device of claim 1, wherein the drug compound has a molecular weight of greater than about 100 kDa.

18. The medical device of claim 17, wherein the drug compound is a protein therapeutic.

19. The medical device of claim 1, wherein the drug compound is a TNF-α

blocker.

20. The device according to claim 1, wherein the channel has a cross-sectional dimension of from about 1 micrometer to about 100 micrometers.

21. The device according to claim 1, wherein the channel has a length of from about 10 micrometers to about 800 micrometers.

22. The device according to claim 1, wherein the microneedle shaft has a length of from about 1 micrometer to about 1 millimeter.

23. The medical device of claim 1, wherein the nanostructures have a height of from about 10 nanometers to about 1 micrometer.

24. The medical device 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 medical device of claim 4, 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.

26. The medical device of claim 4, wherein at least a portion of the nanostructures have a cross-sectional dimension of from about 20 nanometers 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.

27. The medical device of claim 4, where at least a portion of the microstructures have a height of from about 20 nanometers to about 1 micrometer.

28. The medical device of claim 4, wherein at least a portion of the microstructures have an aspect ratio of from about 0.2 to about 5.

29. The medical device of claim 4, wherein at least a portion of the microstructures have an aspect ratio of from about 0.5 to 1.

30. The medical device of claim 4, wherein the cross-sectional dimension of the microstructures is greater than a height of the microstructures.

31. The medical device of claim 4, wherein at least a portion of the nanostructures have a height greater than a cross-sectional dimension.

32. The medical device of claim 4, 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.

33. The medical device of claim 1, wherein the nanostructures are in a form of pillars.

34. The medical device of claim 1, wherein at least a portion of the shaft has a circular cross-section.

35. The medical device of claim 1, wherein at least a portion of the microneedles have a cross-sectional dimension of from about 1 micrometer to about 200 micrometers.