Apparatus and method for the delivery of drugs and genes into tissue

• US 6,192,270 B1
• Filed: 08/14/1998
• Issued: 02/20/2001
• Est. Priority Date: 08/14/1998
• Status: Expired due to Fees

• Current Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Tonnessen, Arnt, Hofmann, Gunter A., Rabussay, Dietmar
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US09/134,245
• Time in Patent Office: 921 Days
• Field of Search: 604/20-21, 607/1-3, 607/72, 607/149, 607/152
• US Class Current: 604/20
• CPC Class Codes: A61N 1/042 Material of the electrode
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/0436 Material of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• 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

An electrode assembly for an apparatus for and a method of trans-surface molecular delivery, including a non-conductive carrier having a proximal surface, a distal surface, and a plurality of through holes from the proximal surface to the distal surface, a first electrode disposed on at least a portion of the distal surface and extending through at least a portion of the plurality of through holes and onto at least a portion of the proximal surface, a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode for engaging a tissue surface through which to apply an electric field, and an insulating barrier that is disposed on at least a portion of the proximal surface of the carrier between the first electrode and the second electrode.

Claims

1. An electrode assembly for electroporation of a tissue surface, comprising:

a non-conductive carrier having a proximal surface, a distal surface, and a first plurality and a second plurality of through holes from the proximal surface to the distal surface;

a first electrode disposed on at least a portion of the distal surface and extending through at least one of the first and second plurality of through holes and onto at least a portion of the proximal surface for engaging the tissue surface through which to apply an electric field; and

a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode adapted for engaging the tissue surface through which to apply an electric field, wherein the through holes enable the passage of a fluid from the distal surface separately to the surface of the respective electrode on the proximal surface.

2. The electrode assembly according to claim 1 wherein the carrier comprises a thin flexible film.

3. The electrode assembly according to claim 1 further comprising an insulating barrier that is disposed on at least a portion of and projecting outward from the proximal surface of the carrier beyond the electrodes for engaging the tissue surface between the first electrode and the second electrode.

4. The electrode assembly according to claim 3 wherein the insulating barrier is a soldermask.

5. The electrode assembly according to claim 1, wherein said first electrode covers substantially the entire distal surface and forms multiple circular portions on said proximal surface;

and

said second electrode covers substantially said entire proximal surface except for the circular portions covered by said first electrode.

6. The electrode assembly according to claim 5, wherein said circular portions are disposed in an array of multiple rows.

7. The electrode assembly of claim 6, wherein said circular portions are in offset rows.

8. An apparatus for trans-surface molecular delivery, comprising:

a first electrode assembly, comprising;

a non-conductive carrier having a proximal surface, a distal surface, and a first and a second plurality of through holes from the proximal surface to the distal surface;

a first electrode disposed on at least a portion of the distal surface and extending through at least one of the first and a second plurality of through holes and onto at least a portion of the proximal surface for engaging a tissue surface through which to apply an electric field; and

a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode for engaging a tissue surface through which to apply an electric field;

a first power supply connected to the first electrode assembly for applying a pulsed electric field of sufficient amplitude to induce pores in the tissue surface; and

means for driving molecules through pores in the tissue surface, wherein the through holes enable the passage of a fluid from the distal surface separately to the surface of the respective electrode on the proximal surface.

9. The electrode assembly according to claim 8, wherein said first electrode covers substantially the entire distal surface and forms multiple circular portions on said proximal surface;

and

said second electrode covers substantially said entire proximal surface except for the circular portions covered by said first electrode.

10. The electrode assembly according to claim 9, wherein said circular portions are disposed in an array of multiple rows.

11. The electrode assembly of claim 9, wherein said circular portions are in offset rows.

12. An apparatus for trans-surface molecular delivery, comprising:

a first electrode assembly, comprising;

a non-conductive carrier having a proximal surface, a distal surface, and a plurality of through holes from the proximal surface to the distal surface;

a first electrode disposed on at least a portion of the distal surface and extending through at least a portion of the plurality of through holes and onto at least a portion of the proximal surface, and

a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode for engaging a tissue surface through which to apply an electric field;

a first power supply connected to the first electrode assembly for applying a pulsed electric field of sufficient amplitude to induce pores in the tissue surface; and

means for driving molecules through pores in the tissue surface, wherein said means for driving comprises;

a second electrode assembly spaced from the first electrode assembly and comprising at least one of an anode and a cathode; and

a second power supply connected to the first electrode assembly and the second electrode assembly for applying a low voltage continuous electric field of a preselected polarity and sufficient amplitude to induce migration of molecules through pores in the tissue surface.

13. An apparatus for trans-surface molecular delivery, comprising:

a first electrode assembly, comprising;

a non-conductive carrier having a proximal surface, a distal surface, and a plurality of through holes from the proximal surface to the distal surface;

a first electrode disposed on at least a portion of the distal surface and extending through at least a portion of the plurality of through holes and onto at least a portion of the proximal surface, and

a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode for engaging a tissue surface through which to apply an electric field;

a first power supply connected to the first electrode assembly for applying a pulsed electric field of sufficient amplitude to induce pores in the tissue surface; and

means for driving molecules through pores in the tissue surface, wherein means for driving comprises a pressure source adapted to be in communication with the tissue surface via the plurality of through holes in the carrier of the first electrode assembly for applying pressure of a sufficient amplitude and duration to induce migration of molecules through pores in the tissue surface.

14. An apparatus for trans-surface molecular delivery, comprising:

a first electrode assembly, comprising;

a non-conductive carrier having a proximal surface, a distal surface, and a plurality of through holes from the proximal surface to the distal surface;

a first electrode disposed on at least a portion of the distal surface and extending through at least a portion of the plurality of through holes and onto at least a portion of the proximal surface, and

a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode for engaging a tissue surface through which to apply an electric field;

a first power supply connected to the first electrode assembly for applying a pulsed electric field of sufficient amplitude to induce pores in the tissue surface; and

means for driving molecules through pores in the tissue surface, wherein means for driving comprises an ultrasound source for applying ultrasound of a sufficient amplitude and duration to induce migration of molecules through pores in the tissue surface.

15. An apparatus for trans-surface molecular delivery, comprising:

a first electrode assembly, comprising;

a non-conductive carrier having a proximal surface, a distal surface, and a plurality of through holes from the proximal surface to the distal surface;

a first electrode disposed on at least a portion of the distal surface and extending through at least a portion of the plurality of through holes and onto at least a portion of the proximal surface, and

a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode for engaging a tissue surface through which to apply an electric field;

a first power supply connected to the first electrode assembly for applying a pulsed electric field of sufficient amplitude to induce pores in the tissue surface; and

means for driving molecules through pores in the tissue surface, means for driving comprises means for electroincorporation of molecules for applying electroincorporation of a sufficient amplitude and duration to induce migration of particles containing molecules through pores in the tissue surface.

16. A method of trans-surface molecular delivery, comprising:

providing a first electrode assembly, comprising;

a non-conductive carrier having a proximal surface, a distal surface, and a first plurality and a second plurality of through holes from the proximal surface to the distal surface;

a first electrode disposed on at least a portion of the distal surface and extending through at least one of the first and second plurality of through holes and onto at least a portion of the proximal surface; and

a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode;

engaging a tissue surface with the first electrode assembly;

introducing molecules through at least one of the first and second plurality of through holes and onto at least a portion of the proximal surface;

providing a first power supply connected to the first electrode assembly;

applying a pulsed electric field via the first electrode assembly of sufficient amplitude to induce pores in the tissue surface;

providing means for driving molecules through pores in the tissue surface; and

applying means for driving to induce migration of molecules through pores in the tissue surface.

17. The method according to claim 16 wherein the step of providing means for driving comprises the steps of:

providing a second electrode assembly spaced from the first electrode assembly and comprising at least one of an anode and a cathode; and

providing a second power supply connected to the first electrode assembly and the second electrode assembly,

and wherein the step of applying means for driving comprises the step of applying a low voltage continuous electric field of a preselected polarity and sufficient amplitude to induce migration of molecules through pores in the tissue surface.

18. The method according to claim 16 wherein the step of providing means for driving comprises the step of providing a pressure source in communication with the tissue surface via the plurality of through holes in the carrier of the first electrode assembly and wherein the step of applying means for driving comprises the step of applying pressure to the first electrode assembly of a sufficient amplitude and duration to induce migration of molecules through pores in the tissue surface.

19. The method according to claim 16 wherein the step of providing means for driving comprises the step of providing an ultrasound source and wherein the step of applying means for driving comprises the step of applying ultrasound of a sufficient amplitude and duration to induce migration of molecules through pores in the tissue surface.

20. The method according to claim 16 wherein the step of providing means for driving comprises the step of providing means for electroincorporation of molecules and wherein the step of applying means for driving comprises the step of applying means for electroincorporation of a sufficient amplitude and duration to induce migration of particles containing molecules through pores in the tissue surface.