Implantable electroporation method and apparatus for drug and gene delivery

• US 5,501,662 A
• Filed: 09/12/1994
• Issued: 03/26/1996
• Est. Priority Date: 05/22/1992
• Status: Expired due to Term

• Current Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: Hofmann, Gunter A.
• Primary Examiner(s): Green, Randall
• Assistant Examiner(s): REICHLE, KARIN M
• Application Number:
  US08/304,584
• Time in Patent Office: 561 Days
• Field of Search: 600/1, 600/2, 600/13, 600/14, 604/890.1, 604/891.1, 604/892.1, 604/20, 604/21, 604/49, 604/52, 604/53, 435/172.2, 435/173.6, 435/287, 435/289, 204/180.1, 204/299 R, 935/52, 128/639, 128/642, 128/644, 607/1-3, 607/65, 607/72, 607/74, 607/98-101, 607/113, 607/115, 607/116, 607/117, 607/144-145, 607/154-156
• US Class Current: 604/20
• 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
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

A method and apparatus are provided for introducing molecules such as genes and pharmacological compounds into living blood cells of a patient for therapeutic purposes. A device is implanted into the body of the patient for generating an electric field at a preselected location within a selected blood vessel. Preselected molecules are infused into the selected blood vessel. Simultaneously an electric signal is applied to the implanted device to repeatedly subject a quantity of blood flowing within the selected blood vessel past the preselected location to electric fields of a predetermined amplitude and duration. The parameters of the electric fields are precisely controlled in order to make the walls of preselected cells in the blood transiently permeable to permit the molecules to enter said preselected cells without killing said cells. The device can include either a pair of electrodes implanted in the blood vessel, or alternatively, an induction coil that surrounds the blood vessel. The electric signal is supplied by a power pack and the preselected molecules are infused with a supply pump.

Claims

1. A method of introducing molecules into living blood cells of a patient for therapeutic purposes, comprising the steps of:

providing an implantable electric field generating device;

implanting said device into a body of the patient at a preselected location within close proximity of a selected blood stream and disposed at least partially around a center of a selected blood vessel through which the selected blood stream flows for generating electric fields at a preselected location within said selected blood vessel;

infusing preselected of said molecules into the selected blood vessel upstream of the preselected location within said selected blood vessel; and

applying an electric signal to the implanted device to cause it to generate electric fields of a predetermined amplitude and duration to repeatedly subject a quantity of blood flowing past the preselected location within the selected blood vessel to said electric fields of a predetermined amplitude and duration in order to make the walls of preselected cells in the blood transiently permeable to permit the molecules to enter said preselected cells without killing said cells.

2. A method according to claim 1 wherein the molecules are selected from the group consisting of genes and pharmacological compounds.

3. A method according to claim 1 wherein the preselected cells are selected from the group consisting of red and white blood cells.

4. A method according to claim 1 wherein the device for generating the electric fields includes a paid pair of spaced apart electrodes mounted inside the selected blood vessel.

5. A method according to claim 1 wherein the device for generating the electric fields includes an induction coil that surrounds the selected blood vessel.

6. A method according to claim 1 wherein the electric signal has a wave form selected from the group consisting of an exponentially decaying pulse, a square pulse, a unipolar oscillating pulse train and a bipolar oscillating pulse train.

7. A method according to claim 1 wherein the electric fields have a strength of between approximately 0.2 kV/cm and 20.0 kV/cm.

8. A method according to claim 6 wherein each pulse has a duration of between approximately ten microseconds and one hundred milliseconds.

9. A method according to claim 6 wherein the electric fields apply between approximately one pulse and one hundred pulses to a given unit of liquid volume as the unit flows past the preselected location in the selected blood vessel.

10. A method according to claim 1 wherein the preselected cells are lymphocytes, the electric fields have a strength of approximately 0.55 kV/cm and the signal has a pulse train wave form that decays exponentially with a pulse duration of approximately fifty to fifty-five milliseconds.

11. An apparatus for introducing molecules in vivo into living blood cells of a patient, comprising:

an implantable electric field generating device sized and shaped to be implanted in the patient at a preselected location in close proximity of a selected blood stream and disposed at least partially around a center of a selected blood vessel through which the selected blood stream flows for generating electric fields at a preselected location within the selected blood vessel of the patient;

means for injecting a predetermined quantity of a fluid medium carrying preselected of said molecules into the selected blood vessel upstream of the preselected location within the selected blood vessel; and

means for applying an electric signal to the implantable device for causing it to repeatedly generate electric fields of a predetermined amplitude and duration in order to make the walls of preselected cells in blood flowing past the preselected location within the selected blood vessel to be transiently permeable to permit the molecules to enter said preselected cells without killing said cells.

12. An apparatus according to claim 11 wherein the means for injecting the quantity of fluid carrying the molecules includes a pump.

13. An apparatus according to claim 11 wherein the means for applying an electric signal to the device includes a signal generator for generating the electric signal.

14. An apparatus according to claim 11 wherein the implantable device includes a pair of spaced apart conductive electrodes sized and shaped for implantation in the patient'"'"'s body so that the blood in the selected blood vessel flows between the electrodes.

15. An apparatus according to claim 14 wherein the pair of conductive electrodes are sized and shaped for implantation in the selected blood vessel and coated with a clot inhibiting material with pores sufficiently large to permit ions to carry a charge between the electrodes.

16. An apparatus according to claim 15 wherein the implantable device further includes a dielectric cylinder surrounding and supporting the electrodes within the selected blood vessel.

17. An apparatus according to claim 16 wherein the electrodes are diametrically spaced apart so that the blood flows through the selected blood vessel.

18. An apparatus according to claim 16 wherein the electrodes are ring-shaped and are spaced apart.

19. An apparatus according to claim 11 wherein the implantable device is a coil sized and shaped for implantation in the patient and surrounding the selected blood vessel.

20. An apparatus according to claim 11 wherein the implantable device is a coil adapted for surrounding the blood vessel and has a serpentine configuration.