Nanopatterned Medical Device with Enhanced Cellular Interaction

• US 20110270221A1
• Filed: 04/27/2011
• Published: 11/03/2011
• 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
• Granted Patent: US 10,245,421 B2
• Time in Patent Office: Days
• US Class Current: 604/506
• 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 comprising an array of microneedles that extend outwardly from a support, wherein at least one of the microneedles contains a plurality of nanostructures formed on a surface thereof, the nanostructures being arranged in a predetermined pattern.

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

3. The medical device of claim 1, 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.

4. 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.

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

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

7. The medical device of claim 6, wherein the microstructures have a cross-sectional dimension of greater than about 500 nanometers and the nanostructures have a cross-sectional dimension of less than about 300 nanometers.

8. The medical device of claim 6, 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.

9. 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.

10. The medical device 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.

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

12. The medical device of claim 1, where at least a portion of the nanostructures have a height of from about 10 nanometers to about 20 micrometers.

13. 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.

14. The medical device of claim 1, wherein at least a portion of the nanostructures have an aspect ratio of from about 0.15 to about 30.

15. The medical device of claim 1, wherein at least a portion of the nanostructures have an aspect ratio of from about 0.2 to about 5.

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

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

18. The medical device of claim 1, wherein the microneedle surface containing the plurality of nanostructures has an average surface roughness between about 10 nanometers and about 200 nanometers.

19. The medical device of claim 1, wherein the microneedle surface containing the plurality of nanostructures has an effective compression modulus between about 4 MPa and about 320 MPa.

20. The medical device of claim 1, wherein the microneedle surface containing the plurality of nanostructures has an effective shear modulus between about 0.2 MPa and about 50 MPa.

21. The medical device of claim 1, wherein the microneedle surface containing the plurality of nanostructures has a water contact angle between about 80°

and about 150°

.

22. The medical device of claim 1, further comprising a reservoir for holding a drug compound.

23. The medical device of claim 22, wherein the drug compound has a molecular weight of greater than about 100 kDa.

24. The medical device of claim 23, wherein the drug compound is a protein therapeutic.

25. The medical device of claim 22, wherein the drug compound is a TNF-α

blocker.

26. The medical device of claim 22, wherein at least one of the microneedles contains a channel for delivering the drug compound.

27. A method for delivering a drug compound to a subdermal location, the method comprising:

penetrating the stratum corneum with a microneedle that is in fluid communication with the drug compound, the microneedle containing a plurality of nanostructures formed on a surface thereof and arranged in a pattern; and

transporting the drug compound through the microneedle and across the stratum corneum.

28. The method of claim 27, further comprising contacting an extracellular matrix protein, a plasma membrane protein, or a combination thereof with the nanostructures.

29. The method of claim 28, wherein the plasma membrane protein is a focal adhesion protein, an endocytosis mediating receptor, or a transmembrane protein.

30. The method of claim 27, wherein the nanostructures change the membrane conductivity of the cell.

31. The method of claim 27, wherein the nanostructures change the structure of an intercellular junction.

32. The method of claim 31, wherein the intercellular junction is a tight junction.

33. The method of claim 27, wherein the drug compound is delivered to the cytoplasm of a cell.

34. The method of claim 27, wherein the drug compound is delivered to the nuclear envelope of a cell.

35. A medical device comprising a plurality of nanostructures that are fabricated on a surface of the medical device, the plurality of nanostructures defining a fabricated nanotopography.

36. The medical device of claim 35, wherein the surface is a surface of a microneedle.

37. The medical device of claim 36, wherein the microneedle is a component of a microneedle assembly.

38. The medical device of claim 35, 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, a center-to-center spacing of from about 50 nanometers to about 1 micrometer, and a height of from about 10 nanometers to about 1 micrometer.

39. A method for forming a medical device comprising fabricating a pattern of nanostructures on a surface of a microneedle.

40. The method of claim 39, wherein the pattern of nanostructures are fabricated according to a techniques selected from the group consisting of photolithography, e-beam lithography, X-ray lithography, self-assembly techniques, reactive ion etching, wet etching, film deposition, sputtering, chemical vapor deposition, epitaxy, electroplating, and combinations thereof.

41. The method of claim 39, wherein the step of fabricating the pattern of nanostructures comprises a nanoimprint lithography technique.