Vaccine delivery via microneedle arrays
View Patent ↗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.
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 μm 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 cm 2 of skin surface.
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/cm 2 of vaccine.
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.