The present invention aims to provide a method for producing a microneedle device comprising a coating comprising dexmedetomidine and isoproterenol, in which the stability of isoproterenol during production and after production of the microneedle device is high. A method for producing a microneedle device according to one embodiment of the present invention comprises coating microneedles with a coating liquid to form a coating on the microneedles. The microneedle device comprises a substrate, microneedles disposed on the substrate, and a coating formed on the microneedles. The coating liquid comprises dexmedetomidine or a pharmaceutically acceptable salt thereof, isoproterenol or a pharmaceutically acceptable salt thereof, ethylenediaminetetraacetic acid or a pharmaceutically acceptable salt thereof, and a sulfated polysaccharide.

The present disclosure relates to a method for manufacturing a microneedle containing a coating part on a needle tip and an apparatus used for the method. When a microneedle is manufactured using the coating method and apparatus according to the present disclosure, a coating part in which a target material is impregnated can be easily inserted into skin and effective dissolution is possible. Further, the target material is allowed to show excellent skin permeability with the dissolution of the coating part of the microneedle manufactured according to the present disclosure, thereby a quantitative amount of target material can be effectively delivered into the skin.

A cold atmospheric plasma (CAP)-mediated ICB therapy/delivery device are disclosed herein that employs a patch having microneedles that are used to deliver the CAP transdermally along with an immune checkpoint inhibitor for enhancing transdermal treatment efficacy. The hollow-structured microneedle patch can facilitate the transportation of CAP through the skin, causing tumor cell death. The release of cancer antigens then promotes the maturation of dendritic cells in the tumor-draining lymph nodes, subsequently initiating the T cell-mediated immune response. Anti-PDL1 antibody (aPDL1), an immune checkpoint inhibitor (or other immune checkpoint inhibitors), released from the microneedle patch (in some embodiments) further augments the anti-tumor immunity. The transdermal combinational CAP and ICB therapy inhibits tumor growth for both primary tumors as well as distant tumors, with prolonged survival in the tumor-bearing mice. Such results should translate to other species.

The present invention provides for microneedle arrays and related systems and methods. Particularly, microneedle arrays that are configured to deliver active agents, including nucleic acids and vaccines, are provided. Additional related methods of vaccinating and minimizing the amount of vaccine necessary for effective inoculation are also provided.

Compositions for coating microneedles with aluminum-adjuvanted vaccines are provided comprising an aluminum-containing wet gel suspension selected from aluminum hydroxide wet gel suspension and aluminum phosphate wet gel suspension; a vaccine in an amount effective to stimulate an immune response in a mammal; a sugar, sugar alcohol, or combinations thereof; and a thickener. Some embodiments of the compositions have a viscosity of 500 to 30,000 cps when measured at 100 s.sup.−1 and temperature of 25 C. Microneedle devices coated with the compositions, as well as methods of forming the compositions and coating the microneedles, and methods of maximizing the aluminum content of vaccine-coated microneedle arrays are also provided.

An article (100) comprising at least one microneedle (160) is provided. The article comprises a first side (112) and a second side (114) opposite the first side. The first side comprises a central cavity portion (120) and a platform portion (130), with at least one microneedle extending therefrom, wherein the platform portion is not coplanar with the central cavity portion. The platform portion substantially surrounds the central cavity portion. The at least one microneedle comprises a body comprising an outer surface (163); a base segment (166) having a base (162) and a first shape; a tip segment (168) having a tip and a second shape, wherein the second shape is distinct from the first shape; a transition plane (167) that delineates the base segment and the tip segment; and a central axis (180). Methods of using the article are also provided.

The present invention provides a microneedle array, a support member, a method of producing a microneedle array, and a microneedle array unit which enable reduction of a drying time during production and prevention of breakage during drying. Provided are a microneedle array 120 including a sheet portion 41, a plurality of needle-like protrusions 44, and a support member 50 formed of a gripping portion 52 and a beam portion 54 having one end that is connected to the gripping portion 52, in which the sheet portion 41 is an integrally molded body which is integrally molded with the support member 50, in which at least a part of the beam portion 54 is buried under the other surface 43 of the sheet portion 41, opposite to the one surface where the needle-like protrusions 44 are provided, the gripping portion 52 is provided on the other surface 43 of the sheet portion 41, and the beam portion 54 is deformable toward a center of the sheet portion 41. Further, provided are the support member 50, a method of producing the microneedle array 120, and a microneedle array unit 300 including a container 310.

A fluid delivery apparatus includes a collet assembly having an upper and lower wall attached at a central portion of the collet. The central portion defines an inner step, and the lower wall includes circumferentially-spaced flexible tabs. The fluid delivery apparatus also includes a fluid distribution assembly coupled to the collet assembly. The fluid distribution assembly is positionable relative to the collet between a pre-use configuration and a pre-activated configuration. The fluid distribution assembly has a plenum that includes a sleeve component having an exterior ledge extending thereabout. A lower wall portion of the sleeve component includes protrusions corresponding to the flexible tabs of the collet. In the pre-use configuration the exterior ledge of the sleeve component is engaged with the inner step of the collet assembly, and each flexible tab engages a respective protrusion to provide a snap-fit between the fluid distribution assembly and the collet assembly.

A microneedle patch applicator housing, being formed from a single sheet or film having a top surface and an undersurface, the housing including a flat peripheral base part and a raised part surround by the peripheral base part and bulging vertically, with respect to the peripheral base part, from the undersurface toward the top surface, an undersurface portion of the raised part forming a surface supporting a microneedle patch, the raised part including a plurality of concavely bent parts, and the concavely bent parts each having a concave bottom toward a direction away from a center portion of the raised part.

The present invention provides a solution to increase the drug loading capacity and drug delivery precision of dissolving microneedles. These solutions include: (a) increasing the base of the microneedle cavities without substantially changing the microneedle's height and geometry, (b) use of drug suspension and sedimentation of drug by centrifugation, and (c) a specific centrifugation order for filling drug and matrix material. In the first preferred embodiment, a microneedle master mould comprising a plurality of pyramidal microneedles (5100), wherein each of the pyramidal microneedles further comprising a chamfered base (5200) which extends to and adjoins with its neighbouring chamfered bases is provided. In the second preferred embodiment, a method of making dissolving microneedles is provided, comprising (a) providing a microneedle template comprising a plurality of pyramidal microneedle cavities, wherein each of the pyramidal microneedle cavities further comprising a chamfered base which extends to and adjoins with its neighbouring chamfered bases; (b) loading a drug suspension in the substrate cavity on the microneedle template; (c) centrifuging the microneedle template which is loaded with a drug suspension, (d) loading a matrix material solution in the substrate cavity on the microneedle template; (d) centrifuging the microneedle template loaded with the drug suspension and the matrix material solution; and (e) drying the centrifuged microneedle template in a controlled environment.