# US 12,214,150 B2 · Microneedle arrays with undercut features for cutaneous and non-cutaneous drug delivery > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,214,150 B2 - Document ID: US12214150B2 - Status: Granted - Kind: B2 - Application number: 17/611,486 - Filed: 2020-05-15 - Published: 2022-08-04 - Granted: 2025-02-04 - Earliest claimed: 2019-05-16 - Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education - Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education - Inventors: Louis D. Falo, Jr.; Emrullah Korkmaz - Web page: https://patentgrep.com/patent/US12214150B2 ## CPC - A61M 37/0015: {by using microneedles} - A61L 31/148: {Materials at least partially resorbable by the body} - A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)} - B29C 33/3835: {Designing moulds, e.g. using CAD-CAM} - B29C 33/3842: {Manufacturing moulds, e.g. shaping the mould surface by machining} - B29C 33/3857: {by making impressions of one or more parts of models, e.g. shaped articles and including possible subsequent assembly of the parts} - B29C 33/3878: {used as masters for making successive impressions} - B29C 33/405: {Elastomers, e.g. rubber (B29C33/50 takes precedence)} - B29C 33/50: elastic {or flexible (for isostatic pressing B29C43/3642)} - A61M 2037/0023: {Drug applicators using microneedles} - A61M 2037/0046: {Solid microneedles} - A61M 2037/0053: {Methods for producing microneedles} - B29K 2105/0035: {Medical or pharmaceutical agents} - B29K 2995/006: Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible - B29K 2995/0062: water-soluble - B29L 2031/7544: {Injection needles, syringes} - B29L 2031/756: {Microarticles, nanoarticles} - 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)} - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - 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 ## Abstract The disclosed methods relate to forming microneedle arrays from a production mold that comprises a flexible mold material. The disclosed methods can be used to reproducibly manufacture undercut dissolvable and coated microneedle arrays with various shapes and structures. ## Claims ### Claim 1 A method of forming a microneedle array comprising: forming a production mold of a flexible material, the production mold comprising a plurality of cavities, with each of the plurality of cavities being shaped to define a plurality of respective microneedles that each have a stem, a microneedle tip, a filleted base, and at least one undercut feature; delivering a biodegradable matrix into each of the plurality of cavities of the production mold to form the stem, microneedle tip, and filleted base of each respective microneedle, wherein at least one bioactive material is incorporated into at least a portion of the biodegradable matrix, the biodegradable matrix comprising a first dissolvable material; forming a backing layer adjacent a lower portion of the stem; and removing the microneedles from the production mold by pulling the microneedles out of the mold, wherein the at least a portion of the biodegradable matrix that includes the at least one bioactive material is delivered into at least the microneedle tip defined by the respective cavities of the production mold, wherein the flexible material has sufficient elasticity to allow for the molded microneedle array to be removed from the production mold in a single pull without damaging the integrity of the shape of the microneedles as defined by the mold, and wherein the backing layer is formed from a conformable material. ### Claim 2 (depends on 1) The method of claim 1, wherein the at least one undercut feature is directly below the microneedle tip. ### Claim 3 (depends on 1) The method of claim 1, wherein the stem is formed from the first dissolvable material. ### Claim 4 (depends on 1) The method of claim 1, wherein the stem is formed from a non-dissolvable material. ### Claim 5 (depends on 1) The method of claim 1, wherein the forming of the plurality of microneedles comprises providing a second dissolvable material into the production mold to form a dissolving layer at a portion of the stem that is adjacent the microneedle tip. ### Claim 6 (depends on 5) The method of claim 5, wherein the second dissolvable material of the dissolving layer is selected from a material that dissolves more quickly than the biodegradable matrix that contains the bioactive material. ### Claim 7 (depends on 1) The method of claim 1, wherein the backing layer is formed from the dissolvable material. ### Claim 8 (depends on 1) The method of claim 1, wherein the backing layer is formed from a non-dissolvable material. ### Claim 9 (depends on 1) The method of claim 1, wherein the first dissolvable material comprises carboxymethylcellulose, trehalose, polyvinylpyrrolidone, maltodextrin, silk, hyaluronic acid, poly(vinyl alcohol), polyethylene glycol, poly(lactic-co-glycolic acid), poly(lactic acid), or a combination thereof. ### Claim 10 (depends on 5) The method of claim 5, wherein the second dissolvable material comprises a small molecular weight, quickly dissolving polymer. ### Claim 11 (depends on 10) The method of claim 10, wherein the second dissolvable material is glucose, trehalose, sucrose, maltodextrin, polyvinylpyrrolidone, or a combination thereof. ### Claim 12 (depends on 1) The method of claim 1, wherein the conformable material is a non-dissolving polymer that can flex, deform, or bend to conform to non-uniform skin topography. ### Claim 13 (depends on 1) The method of claim 1, wherein the at least one bioactive material comprises two or more bioactive materials. ### Claim 14 (depends on 1) The method of claim 1, wherein the one or more bioactive materials comprises cosmetics, dermal-fillers, statins, growth factors, pain killers, anti-histamines, vitamins, anesthetics, anti-aging agents, small molecule drugs, haptens, allergens, anti-inflammatory agents, proteins, peptides, micro vesicles, exosomes, polyplexes (siRNA, shRNA, DNA vector complexes), recombinant viral vectors (i.e., Adenovirus, Lentivirus, Vaccinia Virus, Adeno-Associated Virus, and their different serotypes), monoclonal and polyclonal antibodies, and live or lysed cells. ### Claim 15 (depends on 1) The method of claim 1, wherein the plurality of microneedles has a shape that includes a circular obelisk, a square obelisk, a bevel obelisk, a pyramid on a square stem, an arrowhead shape on a stem, a pyramid head on a square obelisk stem, a conical head on a circular obelisk stem, a square obelisk, a 45° pyramid, or a 30° pyramid. ### Claim 16 (depends on 1) The method of claim 1, wherein the plurality of microneedles further comprises a fillet portion at the intersection of the backing layer and the stem. ### Claim 17 A method of forming a flexible elastomer production mold comprising: generating a 3D model drawing of a microneedle array that includes a plurality of microneedles with at least one undercut feature, at least one fillet feature, and at least one backing layer; forming a master microneedle array from the 3D model drawing using 3D laser printing with a wear-resistant resin; forming a negative elastomer mold from the master microneedle array, wherein the negative elastomer mold comprises microneedle-shaped wells with the at least one undercut feature and the at least one fillet feature; forming at least one replica of the master microneedle array from the negative elastomer mold via UV-curable micromolding; and forming the production mold of the microneedle array using the at least one replica, wherein the production mold is formed of a flexible material. ### Claim 18 (depends on 17) The method of claim 17, wherein the flexible material has sufficient elasticity to allow for a molded microneedle array to be removed from the production mold in a single pull without damaging the integrity of the shape of the plurality microneedles as defined by the production mold. ### Claim 19 (depends on 17) The method of claim 17, wherein the at least one replica includes a plurality of replicas, and the forming of the production mold comprises forming a microneedle array holder and combining the plurality of replicas together on the microneedle array holder. ### Claim 20 (depends on 19) The method of claim 19, wherein the microneedle array holder is formed of a resin material.