Delivery device

• US 8,052,633 B2
• Filed: 07/27/2006
• Issued: 11/08/2011
• Est. Priority Date: 01/30/2004
• Status: Active Grant

• Current Assignee: Vaxxas Pty Ltd.
• Original Assignee: Mark Anthony Fernance Kendall
• Inventors: Kendall, Mark Anthony Fernance
• Primary Examiner(s): LAM, ANN Y
• Application Number:
  US11/496,053
• Publication Number:
  US 20110245776A1
• Time in Patent Office: 1,930 Days
• Field of Search: None
• US Class Current: 604/19
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

Abstract

A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest. The device includes a number of projections for penetrating a body surface, with the number of projections being selected to produce a desired response, and the number being at least 500. A spacing between projections is also at least partially determined based on an arrangement of the targets within the body.

Claims

1. A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the device including a number of projections for penetrating a body surface, and wherein:

a) the projections include a targeting section for delivering the material or stimulus to the targets to thereby cause the desired response and a support section for supporting the targeting section;

b) the number of projections is selected to deliver material or stimulus to a number of targets that is at least sufficient to produce the desired response, the number of projections being at least 500;

c) a spacing between projections is at least partially determined based on an arrangement of the targets within the body, the spacing between at least some of the projections being selected to be greater than a diameter of a target of interest; and

d) at least part of at least some of the projections are coated with a non-liquid material.

2. A device according to claim 1, wherein the number of projections is selected by:

a) determining a likelihood of a projection targeting at least one of the targets;

b) determining a number of targets to be targeted; and

,

c) determining the number of projections using the determined likelihood and the determined number of targets.

3. A device according to claim 2, wherein the likelihood of a projection targeting a target of interest is P_contact and is at least partially based on:

4. A device according to claim 2, wherein the number of targets to be targeted depends on the number of targets that need to be transfected to produce the desired response.

5. A device according to claim 4, wherein the number of targets to be targeted is at least one of:

a) at least 10;

b) at least 100;

c) at least 1000;

d) at least 10000;

e) at least 100000;

f) at least 1000000; and

,

g) at least 10000000.

6. A device according to claim 1, wherein the number of projections is at least one of:

a) at least 1000;

b) at least 10000;

c) at least 100000;

d) at least 1000000; and

,

e) at least 10000000.

7. A device according to claim 1, wherein a maximum number of projections is based on at least one of:

a) the total surface area of the target site available;

b) a minimum projection spacing (S); and

,

c) an upper limit in active material or stimulus to be delivered.

8. A device according to claim 1, wherein the projection spacing is based at least partially on at least one of:

a) a size of the targets of interest; and

,

b) a spacing between the targets of interest.

9. A device according to claim 1, wherein the spacing between at least some of the projections is selected to avoid multiple projections targeting a single target of interest.

10. A device according to claim 1, wherein the spacing between at least some of the projections is selected to be approximately equal to the spacing between the targets of interest.

11. A device according to claim 1, wherein the projection spacing (S) is at least one of:

a) 1 μ

m≦

S≦

10000 μ

m; and

,

b) 10 μ

m≦

S≦

200 μ

m.

12. A device according to claim 1, wherein projection dimensions are based at least partially on an arrangement of targets within the body.

13. A device according to claim 12, wherein at least some of the projections have a diameter of at least one of:

a) less than the size of targets; and

,

b) substantially equal to the size of targets within the targets.

14. A device according to claim 12, wherein at least some of the projections have a projection length at least partially based on a depth of the targets below a surface of the body against which the device is to be applied in use.

15. A device according to claim 12, wherein at least some of the projections within a targeting configuration have different dimensions.

16. A device according to claim 1, wherein the targeting section has a diameter of less than at least one of:

a) 5 μ

m;

b) 2 μ

m;

c) 1 μ

m; and

,

d) 0.5 μ

m.

17. A device according to claim 1, wherein a length for the targeting section is at least:

a) less than 0.5 μ

m;

b) less than 1.0 μ

m;

c) less than 2.0 μ

m; and

,

d) less than 20 μ

m.

18. A device according to claim 1, wherein a length for the support section is at least partially based on a depth of the targets below a surface of the body against which the device is to be applied in use.

19. A device according to claim 18, wherein the length for the support section is at least partially determined in accordance with properties of a surface of the body against which the device is to be applied in use.

20. A device according to claim 19, wherein a length for the support section is at least one of:

a) for epidermal delivery <

200 μ

m;

b) for dermal cell delivery <

1000 μ

m;

c) for mucosal delivery >

100 μ

m;

d) for delivery to basal cells in the epithelium of the mucosa 600-800 μ

m; and

,

e) for lung delivery of the order of 100 μ

m.

21. A device according to claim 19, wherein the support section penetrates the body surface in use to thereby position the targeting section of at least some of the projections substantially at the depth of the targets below the surface of the body.

22. A device according to claim 1, wherein at least one of a support section length and the number of projections is at least partially based on a likelihood of a projection penetrating the targets at a defined depth (P_depth):

23. A device according to claim 1, wherein the length of the targeting section is greater than the target dimension.

24. A device according to claim 1, wherein the projections are solid.

25. A device according to claim 1, wherein the projections are non-porous and non-hollow.

26. A device according to claim 1, wherein at least part of at least some of the projections are coated with a bioactive material.

27. A device according to claim 1, wherein at least part of a targeting section of at least some of the projections are coated.

28. A device according to claim 1, wherein the coating is at least one of:

a) nanoparticles;

b) a nucleic acid or protein;

c) an antigen, allergen, or adjuvant;

d) parasites, bacteria, viruses, or virus-like particles;

e) quantum dots, SERS tags, raman tags or other nanobiosensors;

f) metals or metallic compounds; and

,

g) molecules, elements or compounds.

29. A device according to claim 1, wherein each of the number of projections is for penetrating the body surface.

30. A device according to claim 1, wherein the targets of interest are at least one of antigen-presenting cells, antigen-presenting cell organelles and antigen-presenting cell nuclei.

31. A device according to claim 1, wherein the desired response is at least one of an immune response and a tolerogenic response.

32. A device according to claim 1, wherein the device is a patch including a base and an array of projections extending substantially perpendicularly from the base, each projection including a tip for penetrating the body surface.

33. A device according to claim 1, wherein at least some of the projections perturb the targets in use to thereby induce bystander responses.

34. Apparatus for delivery of material or stimulus to targets of interest within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the apparatus including:

a) a structure;

b) a plurality of projections movably mounted to the structure for penetrating a body surface;

c) an actuator for selectively releasing the plurality of projections mounted on the movable structure from a retracted position such that upon contact with the body surface the plurality of projections enter the body, the actuator including;

i) a spring coupled to the structure and the at least one patch;

ii) a releasing means for releasing the spring, to thereby release the plurality of projections from the retracted position; and

,

iii) a number of arms, each arm being coupled to a respective spring and including a first end pivotally mounted to the structure and a second end coupled to a respective plurality of projections, and wherein activation of the releasing means causes each of the arms to be released from a retracted position to thereby cause projections on the respective patch to enter the body.

35. Apparatus according to claim 34, wherein the plurality of projections are provided on a patch.

36. Apparatus according to claim 34, wherein the releasing means is a tensioned string for holding the spring in compression.

37. Apparatus according to claim 34, wherein the releasing means is manually operated.

38. Apparatus according to claim 34, wherein the arms are circumferentially spaced around a part of the structure.

39. Apparatus according to claim 34, wherein the structure is flexible structure allowing the structure to be guided to a desired location within the body.

40. Apparatus according to claim 34, wherein the releasing means includes an inflatable structure coated with the plurality of projections.

41. Apparatus according to claim 34, wherein:

a) the number of projections is selected to produce a desired response, the number being at least 500; and

,

b) a spacing between projections is at least partially determined based on an arrangement of the targets within the body.

42. A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the device including a number of projections for penetrating a body surface, and wherein:

a) the number of projections is selected to deliver material or stimulus to a number of targets that is at least sufficient to produce the desired response, the number of projections being at least 500;

b) a spacing between projections is at least partially determined based on an arrangement of the targets within the body, the spacing between at least some of the projections being selected to be greater than a diameter of a target of interest; and

,

c) the device includes at least some uncoated projections to thereby stimulate or perturb the targets in use.

43. A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the device including a number of projections for penetrating a body surface, and wherein:

a) at least part of at least some of the projections are coated with a non-liquid bioactive material for delivery to the targets, to thereby cause the desired response;

b) the number of projections is selected to deliver material or stimulus to a number of targets that is at least sufficient to produce the desired response, the number of projections being at least 500; and

c) a spacing between projections is at least partially determined based on an arrangement of the targets within the body, the spacing between at least some of the projections being selected to be greater than a diameter of a target of interest.

44. A device according to claim 43, wherein at least part of at least some of the projections are coated with two or more different non-liquid materials on the same projection.

45. A device according to claim 43, wherein at least some of the targets are at least one of antigen-presenting cells, antigen-presenting cell organelles and antigen-presenting cell nuclei, and the desired response being at least one of an immune response and a tolerogenic response.

46. A device according to claim 43, wherein at least some of the targets are at least one of:

a) macrophages;

b) monocytes;

c) B lymphocytes;

d) monocytic-granulocytic-DC precursors;

e) marginal zone Kupffer cells;

f) microglia;

g) T cells;

h) Langerhans cells;

i) dendritic cells;

j) activated T lymphocytes;

k) eosinophils;

l) keratinocytes;

m) astrocytes;

n) follicular cells;

o) microglial cells;

p) thymic cortical cells;

q) endothelial cells;

r) Schwann cells;

s) retinal pigment epithelial cells;

t) myoblasts;

u) vascular smooth muscle cells;

v) chondrocytes;

w) enterocytes;

x) thymocytes;

y) kidney tubule cells; and

,

z) fibroblasts.

47. A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the device including a number of projections for penetrating a body surface, and wherein:

a) the number of projections is selected to deliver material or stimulus to a number of targets that is at least sufficient to produce the desired response, the number of projections being at least 500;

b) a spacing between projections is at least partially determined based on an arrangement of the targets within the body, the spacing between at least some of the projections being selected to be greater than a diameter of a target of interest; and

,

c) at least part of at least some of the projections dissolve upon penetrating the body surface.

48. A device according to claim 47, wherein a bioactive material is releasably incorporated into the projections to thereby allow the bioactive material to be delivered to the targets as the at least part of at least some of the projections dissolve.

49. A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the device including a number of projections for penetrating a body surface, and wherein:

a) the number of projections is selected to deliver material or stimulus to a number of targets that is at least sufficient to produce the desired response, the number of projections being at least 500;

b) a spacing between projections is at least partially determined based on an arrangement of the targets within the body, the spacing between at least some of the projections being selected to be greater than a diameter of a target of interest; and

,

c) at least some of the projections have dimensions that are different to corresponding dimensions of at least some other projections of the device.

50. A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the device including a number of projections for penetrating a body surface, and wherein:

a) the projections include a targeting section for delivering the material or stimulus to the targets to thereby cause the desired response and a support section for supporting the targeting section;

b) the number of projections is selected to deliver material or stimulus to a number of targets that is at least sufficient to produce the desired response, the number of projections being at least 500;

c) a spacing between projections is at least partially determined based on an arrangement of the targets within the body, the spacing between at least some of the projections being selected to be greater than a diameter of a target of interest;

d) projection dimensions are based at least partially on an arrangement of targets within the body; and

,

e) at least some of the projections within a targeting configuration have different dimensions.

51. A device for delivery of material or stimulus to targets within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the device including a number of projections for penetrating a body surface, and wherein:

a) the projections include a targeting section for delivering the material or stimulus to the targets to thereby cause the desired response and a support section for supporting the targeting section;

b) the number of projections is selected to deliver material or stimulus to a number of targets that is at least sufficient to produce the desired response, the number of projections being at least 500; and

,

c) a spacing between projections is at least partially determined based on an arrangement of the targets within the body, the spacing between at least some of the projections being selected to be greater than a diameter of a target of interest;

d) at least some of the projections perturb the targets in use to thereby induce bystander responses.

52. Apparatus for delivery of material or stimulus to targets of interest within a body to produce a desired response, the targets being at least one of cells of interest, cell organelles of interest and cell nuclei of interest, the apparatus including:

a) a structure;

b) a plurality of projections movably mounted to the structure for penetrating a body surface; and

c) an actuator for selectively releasing the plurality of projections mounted on the movable structure from a retracted position such that upon contact with the body surface the plurality of projections enter the body, the actuator including a releasing means for releasing the plurality of projections from the retracted position, the releasing means including an inflatable structure coated with the plurality of projections.