Transdermal delivery of therapeutic agent

• US 20050273046A1
• Filed: 06/03/2004
• Published: 12/08/2005
• Est. Priority Date: 06/03/2004
• Status: Active Grant

• Current Assignee: Lynntech Incorporated
• Original Assignee: Lynntech Incorporated
• Inventors: Hayes, Ryan T., Kwiatkowski, Krzysztof C., Magnuson, James W., Giletto, Anthony
• Granted Patent: US 7,315,758 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428

Abstract

A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

Claims

1. A device for transdermal delivery of a therapeutic agent to a biological subject, comprising:

a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections;

a reservoir for holding the therapeutic agent surrounding the first electrode;

a pulse generator for providing an exponential decay pulse between the first and second electrodes; and

an electronic control module.

2. The device of claim 1, further comprising a second reservoir for holding a second therapeutic agent surrounding the second electrode.

3. The device of claim 2, wherein the second therapeutic agent is the same therapeutic agent surrounding the first electrode.

4. The device of claim 2, further comprising a buffer gel contained in the reservoirs for suspending the therapeutic agents.

5. The device of claim 4, wherein the buffer gel is an agarose gel.

6. The device of claim 4, wherein the buffer gel is selected from iontophoretic gels.

7. The device of claim 2, wherein the buffer gel in the first reservoir is the same material as the buffer gel in the second reservoir.

8. The device of claim 1, wherein the microprojections are adapted to provide perforation of the epidermis to a depth of between about 50 μ

m and about 150 μ

m.

9. The device of claim 1, wherein the microprojections are adapted to transiently perforate the epidermis to a depth greater than the thickness of a stratum corneum layer of the epidermis but less than a depth of sensory nerve ending locations.

10. The device of claim 1, wherein the tip of the microprojections have a diameter of between about 0.5 μ

m and about 5 μ

m.

11. The device of claim 1, wherein the tip of the microprojections have a diameter of between about 1 μ

m and about 2 μ

m.

12. The device of claim 1, wherein the microprojections are made of materials selected from tungsten, platinum, silicon, gold or silver.

13. The device of claim 1, wherein the microprojections are made of etched tungsten wire plated with platinum or gold.

14. The device of claim 1, wherein the microprojections are made of etched silicon block plated with platinum.

15. The device of claim 1, wherein the microprojections are made of silicon.

16. The device of claim 15, wherein the microprojections are plated with platinum or gold.

17. The device of claim 15, wherein the microprojections are plated with a metal.

18. The device of claim 1, wherein each of the arrays measure between about 5 to 10 microprojections by about 5 to 10 microprojections.

19. The device of claim 1, wherein each of the arrays measure between about 1 to 4 microprojections by about 1 to 4 microprojections.

20. The device of claim 1, wherein each of the electrodes further comprise a conductive mount for securing the micro projections in an arranged layout of the array.

21. The device of claim 20, wherein the conductive mount is a conductive mounting rod.

22. The device of claim 20, wherein the conductive mount is a conductive mounting plate.

23. The device of claim 20, wherein the conductive mount comprises a silicon substrate plated with a conductive coating.

24. The device of claim 20, wherein the conductive mount comprises a nonconductive substrate plated with a conductive coating.

25. The device of claim 24, wherein the nonconductive substrate is selected from polyvinylidene fluoride or polyethylene terephthalate.

26. The device of claim 24, wherein the conductive coating is a noble metal.

27. The device of claim 1, further comprising a power source.

28. The device of claim 27, wherein the power source is one or more batteries.

29. The device of claim 28, further comprising a power inverter for transforming DC current from the one or more batteries to AC current to the electrodes.

30. The device of claim 1, wherein the therapeutic agents are microencapsulated within a polymer matrix.

31. The device of claim 30, wherein the polymer matrix is a synthetic cationic copolymer.

32. The device of claim 30, wherein the polymer matrix is a synthetic anionic copolymer.

33. The device of claim 30, wherein the polymer matrix is formed of materials selected from collagen or albumin.

34. The device of claim 30, wherein the therapeutic agents are microencapsulated within micro spheres.

35. The device of claim 34, wherein the microspheres are between about 5 microns and about 100 microns.

36. The device of claim 34, wherein the microspheres have a diameter of between about 10 microns and about 70 microns.

37. The device of claim 30, wherein the therapeutic agent is negatively charged, the therapeutic agent is selectively microencapsulated within a polymer matrix that is negatively charged, positively charged, or has no charge.

38. The device of claim 30, wherein the therapeutic agent is positively charged, the therapeutic agent is selectively microencapsulated within a polymer matrix that is negatively charged, positively charged, or has no charge.

39. The device of claim 30, wherein the therapeutic agent has no charge, the therapeutic agent is selectively microencapsulated within a polymer matrix that is negatively charged, positively charged, or has no charge.

40. The device of claim 1, wherein the exponential decay pulse is superimposed over a sign wave current.

41. The device of claim 1, wherein the exponential decay pulse is superimposed over a constant current function to offset the constant current function to a net negative or a net positive current.

42. A method for transdermal delivery of a therapeutic agent, comprising:

piercing a stratum corneum layer of skin with two arrays of conductive microprojections;

encapsulating the therapeutic agent into biocompatible charged carriers;

disposing the conductive microprojections into contact with the therapeutic agent;

generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field; and

electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

43. The method of claim 42, wherein the exponential decay pulse is generated using parameters comprising a number of pulses, a voltage range, and a time period.

44. The method of claim 43, wherein the number of pulses are between about 100 and 300 per minute.

45. The method of claim 43, wherein the voltage range is between about 60 V and about 3 V.

46. The method of claim 43, wherein the upper voltage of the voltage range is between about 70 V and about 30 V.

47. The method of claim 43, wherein the lower voltage of the voltage range is between about 20 V and about 0.5 V.

48. The method of claim 43, wherein the time period is between about 30 seconds and about 1 second.

49. The method of claim 43, wherein the time period is between about 10 seconds and about 2 seconds.