Implantable Devices for Delivery of Bioactive Agents

• US 20140287019A1
• Filed: 10/16/2012
• Published: 09/25/2014
• Est. Priority Date: 10/27/2011
• Status: Active Grant

• Current Assignee: Sorrento Therapeutics Inc.
• Original Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Inventors: Ross, Russell F., Ollerenshaw, Jeremy, Reichart, Emily
• Granted Patent: US 11,110,066 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2002/0081 directly machined on the prosthetic surface, e.g. holes, grooves A61F2/30771 takes precedence
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

An implantable delivery device and method for utilizing the device to delivery a bioactive agent to a subject in need thereof is described. The device includes a pattern of structures fabricated on a surface of the device 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. The device may be located adjacent tissue such as an endovascular implant or a perivascular implant, and may deliver the bioactive agent without triggering an immune or foreign body response to the bioactive agent.

Claims

1. An implantable delivery device for delivery of a bioactive agent to a subject, the device comprising

a plurality of nanostructures fabricated on a surface of the implantable delivery device, the nanostructures being arranged in a predetermined pattern;

and

a bioactive agent within or on the implantable delivery device.

2. The implantable delivery device according to claim 1, wherein the bioactive agent is a component of a composition, the composition further comprising one or more pharmaceutically acceptable excipients.

3. The implantable delivery device according to claim 1, wherein the pattern further includes microstructures, wherein the nanostructures have a cross-sectional dimension smaller than the microstructures.

4. The implantable delivery device according to claim 3, 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.

5. The implantable delivery device according to claim 3, 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 implantable delivery device according to 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.

7. The implantable delivery device according to claim 1, wherein the pattern has a fractal dimension of greater than about 1.

8. The implantable delivery device according to claim 1, wherein the surface containing the plurality of nanostructures has an average surface roughness between about 10 nanometers and about 200 nanometers and/or an effective compression modulus between about 4 MPa and about 320 MPa.

9. The implantable delivery device according to claim 1, the device comprising a reservoir, wherein the bioactive agent is contained within the reservoir.

10. The implantable delivery device according to claim 1, the device comprising a groove on a surface of the device, wherein the bioactive agent is contained within the groove.

11. A method for forming the implantable delivery device of claim 1, the method comprising fabricating the pattern of nanostructures on the surface of the device.

12. The method according to claim 11, 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.

13. The method according to claim 11, wherein the pattern of nanostructures are fabricated on a film, the method further comprising applying the film to the surface of the implantable delivery device.

14. The method according to claim 11, the method further comprising placing a bioactive agent within or on the device.

15. The implantable delivery device according to claim 1, wherein at least a portion of the nanostructures have a height of from about 10 nanometers to about 20 micrometers.

16. The implantable delivery device according to claim 1, wherein at least a portion of the nanostructures have an aspect ratio of from about 0.15 to about 30.

17. The implantable delivery device according to claim 1, the composition further comprising a sustained release matrix.