# US 10,245,421 B2 · Nanopatterned medical device with enhanced cellular interaction > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,245,421 B2 - Document ID: US10245421B2 - Status: Granted - Kind: B2 - Application number: 13/095,489 - Filed: 2011-04-27 - Published: 2011-11-03 - Granted: 2019-04-02 - Earliest claimed: 2010-04-28 - Assignees: Sorrento Therapeutics, Inc. - Applicants: Russell Frederick Ross - Inventors: Russell Frederick Ross - Web page: https://patentgrep.com/patent/US10245421B2 ## CPC - A61M 37/0015: {by using microneedles} - A61B 17/205: {Vaccinating by means of needles or other puncturing devices} - A61K 9/0021: {Intradermal administration, e.g. through microneedle arrays or needleless injectors} - 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)} - A61K 38/1793: {for cytokines; for lymphokines; for interferons} - A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta} - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - B29C 59/002: {Component parts, details or accessories; Auxiliary operations} - B29C 59/026: {of layered or coated substantially flat surfaces} - A61M 2037/0023: {Drug applicators using microneedles} - A61M 2037/003: {having a lumen} - A61M 2037/0038: {having a channel at the side surface} - A61M 2037/0053: {Methods for producing microneedles} - A61M 2037/0061: {Methods for using microneedles} - B29C 2059/023: {Microembossing} - B29K 2995/0056: Biocompatible, e.g. biopolymers or bioelastomers - B29L 2031/7544: {Injection needles, syringes} - B29L 2031/756: {Microarticles, nanoarticles} - Y10T 156/10: Methods of surface bonding and/or assembly therefor - Y10T 156/1039: Surface deformation only of sandwich or lamina [e.g., embossed panels] - Y10T 156/1057: Subsequent to assembly of laminae - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00) - B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS - B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## 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 ### Claim 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. ### Claim 2 (depends on 1) 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. ### Claim 3 (depends on 1) The medical device of claim 1, wherein the nanostructures have approximately the same cross-sectional dimension. ### Claim 4 (depends on 1) The medical device of claim 1, wherein the pattern further includes microstructures, wherein the nanostructures have a cross-sectional dimension smaller than the microstructures. ### Claim 5 (depends on 4) 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. ### Claim 6 (depends on 4) 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. ### Claim 7 (depends on 1) 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. ### Claim 8 (depends on 1) 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. ### Claim 9 (depends on 1) The medical device of claim 1, wherein at least a portion of the nanostructures have an equidistant spacing. ### Claim 10 (depends on 1) 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. ### Claim 11 (depends on 1) The medical device of claim 1, wherein the pattern has a fractal dimension of greater than about 1. ### Claim 12 (depends on 1) The medical device of claim 1, wherein the pattern has a fractal dimension of from about 1.5 to about 2.5. ### Claim 13 (depends on 1) The medical device of claim 1, wherein the external surface has an average surface roughness between about 10 nanometers and about 200 nanometers. ### Claim 14 (depends on 1) The medical device of claim 1, wherein the external surface has an effective shear modulus between about 4 MPa and about 320 MPa. ### Claim 15 (depends on 1) The medical device of claim 1, wherein the external surface has an effective compression modulus between about 0.2 MPa and about 50 MPa. ### Claim 16 (depends on 1) The medical device of claim 1, wherein the external surface has a water contact angle between about 80° and about 150°. ### Claim 17 (depends on 1) The medical device of claim 1, wherein the drug compound has a molecular weight of greater than about 100 kDa. ### Claim 18 (depends on 17) The medical device of claim 17, wherein the drug compound is a protein therapeutic. ### Claim 19 (depends on 1) The medical device of claim 1, wherein the drug compound is a TNF-α blocker. ### Claim 20 (depends on 1) The device according to claim 1, wherein the channel has a cross-sectional dimension of from about 1 micrometer to about 100 micrometers. ### Claim 21 (depends on 1) The device according to claim 1, wherein the channel has a length of from about 10 micrometers to about 800 micrometers. ### Claim 22 (depends on 1) The device according to claim 1, wherein the microneedle shaft has a length of from about 1 micrometer to about 1 millimeter. ### Claim 23 (depends on 1) The medical device of claim 1, wherein the nanostructures have a height of from about 10 nanometers to about 1 micrometer. ### Claim 24 (depends on 1) 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. ### Claim 25 (depends on 4) 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. ### Claim 26 (depends on 4) 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. ### Claim 27 (depends on 4) 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. ### Claim 28 (depends on 4) 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. ### Claim 29 (depends on 4) 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. ### Claim 30 (depends on 4) The medical device of claim 4, wherein the cross-sectional dimension of the microstructures is greater than a height of the microstructures. ### Claim 31 (depends on 4) The medical device of claim 4, wherein at least a portion of the nanostructures have a height greater than a cross-sectional dimension. ### Claim 32 (depends on 4) 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. ### Claim 33 (depends on 1) The medical device of claim 1, wherein the nanostructures are in a form of pillars. ### Claim 34 (depends on 1) The medical device of claim 1, wherein at least a portion of the shaft has a circular cross-section. ### Claim 35 (depends on 1) 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.