Vaccine delivery via microneedle arrays

• US 8,911,749 B2
• Filed: 10/10/2008
• Issued: 12/16/2014
• Est. Priority Date: 04/16/2007
• Status: Active Grant

• Current Assignee: Corium Pharma Solutions, Inc.
• Original Assignee: Corium International, Inc.
• Inventors: Wendorf, Janet, Williams, Steve, Singh, Parminder, Worsham, Robert Wade, Trautman, Joseph C., Bayramov, Danir, Bowers, Danny Lee, Klemm, Steven Richard, Chen, Guohua, Ghartey-Tagoe, Esi, Klemm, Andy
• Primary Examiner(s): Swartz, Rodney P
• Application Number:
  US12/249,795
• Publication Number:
  US 20090155330A1
• Time in Patent Office: 2,258 Days
• Field of Search: None
• US Class Current: 424/246.1
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/07 Bacillus
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A microprojection array is provided, comprising an approximately planar base and a plurality of microprojections, wherein the array comprises a vaccine and a polymeric material. The array may have multiple layers. The vaccine may be placed in only one layer. In another embodiment of the invention, a method of preventing a disease is provided, comprising insertion into the skin of a patient an array of microprojections comprising a layer which comprises a vaccine for that disease and a polymer.

Claims

1. A microprotrusion array, comprising:

an approximately planar base and a plurality of microprotrusions, each microprotrusion having an attachment point to the base and a distal tip to penetrate skin, said plurality of microprotrusions comprised of a first layer and a second layer, said first layer comprising at least one polymer different from a polymer in the second layer,

the first layer comprised of (i) a biodegradable polymeric material, (ii) a component selected from a sugar, a sugar alcohol, a cyclodextrin, and a water-swellable polymer, and (iii) a vaccine against anthrax, said first layer disposed in at least the distal tip of each microprotrusion in the plurality of microprotrusions, and

wherein the biodegradable polymeric material has a molecular weight of at least about 10,000 Daltons.

2. The array of claim 1, wherein the vaccine lacks an adjuvant.

3. The array of claim 1, wherein at least some of the plurality of microprotrusions detach upon insertion into skin.

4. The array of claim 1, wherein the second layer is comprised of a biodegradable polymeric material selected from poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and polyvinyl alcohol (PVA).

5. The array of claim 4, wherein the polyvinyl alcohol is 0-90% hydrolyzed.

6. The array of claim 1, wherein the sugar is selected from dextrose, fructose, galactose, maltose, maltulose, iso-maltulose, mannose, lactose, lactulose, sucrose and trehalose.

7. The array of claim 1, wherein the first layer further comprises a bioadhesive polymer and wherein the first layer adheres to human skin.

8. The array of claim 1, wherein the array is produced by a process comprising solvent casting.

9. The array of claim 1, wherein the concentration of the vaccine is at least 0.1% by weight of solids of a casting formulation from which the first layer is formed.

10. The array of claim 9, wherein the concentration of the vaccine is at least 5% by weight of solids of a casting formulation from which the first layer is formed.

11. The array of claim 1, wherein the microprotrusions are detachable from the planar base such that, once inserted into skin, the detached microprotrusions provide a depot of the vaccine.

12. The array of claim 1, wherein the first layer is homogeneous.

13. The array of claim 1, wherein the microprotrusions are no more than about 500 μ

m in height.

14. The array of claim 1, wherein the array is flexible.

15. The array of claim 1, wherein the component is a sugar or a sugar alcohol that is present in an amount such that a stability of the vaccine after one year of storage is comparable or greater than that of the same vaccine in aqueous solution in a closed vial.

16. The array of claim 1, wherein the vaccine and the polymeric material are cross-linked by hydrogen bonding.

17. A method of administering a vaccine against anthrax, comprising:

inserting into the skin of a patient an array according to claim 1.

18. The method of claim 17, wherein the vaccine lacks an adjuvant.

19. The method of claim 17, wherein the microprojections are left in the skin for no more than 30 minutes.

20. The method of claim 17, wherein the array is applied to the patient'"'"'s skin by means of an applicator.

21. The method of claim 17, wherein the applicator is spring-loaded.

22. A method of preventing a disease caused by anthrax, comprising introducing into the skin at least about 50 discrete deposits comprising a vaccine against anthrax and a biodegradable polymer using the array according to claim 1.

23. The method of claim 22, wherein the discrete deposits are projections which form part of an array.

24. The method of claim 23, wherein the projections detach from the array.

25. The method of claim 22, wherein each discrete deposit comprises at least about 0.05 ng of vaccine.

26. The method of claim 22, where the initial concentration of vaccine in each discrete deposit is at least about 0.5% by weight.

27. The method of claim 22, wherein where the initial concentration of vaccine in each discrete deposit is at least about 5% by weight.

28. The method of claim 22, wherein the polymer and the vaccine are mixed together within each deposit.

29. The method of claim 22, wherein the discrete deposits are at a density no lower than about 50 deposits per cm² of skin surface.

31. A kit comprising a microprotrusion array as in claim 1 and an applicator for inserting the microprotrusion array into human skin.

32. The array of claim 1, wherein the sugar alcohol is selected from sorbitol, lactitol, maltitol, and mannitol.

33. The array of claim 1, wherein the first layer is comprised of a biodegradable polymeric material selected from dextran and tetrastarch.

34. The array of claim 1, wherein the biodegradable polymeric material is dextran and the component is sorbitol.

30. A microprotrusion array, comprising:

an approximately planar base and a plurality of microprotrusions, wherein the microprotrusions are formed from a biodegradable polymeric material having a molecular weight of at least about 10,000 Daltons that comprises approximately 0.1-50% by weight of solids of a vaccine against anthrax to deliver at least about 2 ng/cm² of vaccine.