Method and apparatus for intracellular delivery of an agent

• US 6,625,486 B2
• Filed: 04/11/2001
• Issued: 09/23/2003
• Est. Priority Date: 04/11/2001
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Aldridge, Elisa J., Lundkvist, Andre-Jean S., Bhat, Vinayak D., Slater, Renee C.
• Primary Examiner(s): Look, Edward K.
• Assistant Examiner(s): Fristoe, Jr., John K.
• Application Number:
  US09/833,149
• Publication Number:
  US 20020151866A1
• Time in Patent Office: 895 Days
• Field of Search: 604/19, 604/20, 604/21
• US Class Current: 604/21
• CPC Class Codes: A61M 2025/0087 Multiple injection needles protruding laterally from the distal tip
• 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 method and an apparatus for electropermeabilization-mediated intracellular delivery of an agent are provided.

Claims

1. A method of delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes into a body lumen;

extending said needle electrodes out from said catheter causing said needle electrodes to penetrate into the tissue surrounding said body lumen;

introducing an agent through at least one of said needle electrodes to said tissue; and

applying an electric field to said tissue by said pair of needle electrodes.

2. The method of claim 1, wherein said applying an electric field causes formation of pores in the cell membranes of the cells of said tissue, wherein said agent passes through said pores into the cells.

3. The method of claim 1, wherein said introducing an agent and said applying an electric field are performed substantially contemporaneously.

4. The method of claim 1, wherein said body lumen is a blood vessel.

5. The method of claim 1, wherein said agent is selected from a group of antiproliferative, antineoplastic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, and antioxidant substances and combinations thereof.

12. The method of claim 4, wherein said pulses are of a duration of between approximately 10 microseconds to approximately 100 milliseconds per pulse.

6. An apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen; and

a pair of needle electrodes integrated with said catheter assembly, said needle electrodes capable of being extended out from said catheter assembly to penetrate into tissue of said treatment site;

wherein said pair of needle electrodes are capable of being in electrical communication with a generator for applying an electric field to said tissue of said treatment site, and wherein at least one needle electrode of said pair of needle electrodes allows for injection of an agent to said tissue of said treatment site.

7. The apparatus of claim 6, wherein one of said pair of needle electrodes is configured to receive a first charge and the other of said pair of needle electrodes is configured to receive a second charge different from said first charge.

8. The apparatus of claim 6, wherein said electric field increases the permeability of the cell membranes of cells at said treatment site.

9. The apparatus of claim 6, wherein said catheter assembly comprises at least one inflatable balloon.

10. The apparatus of claim 6, wherein said needle electrodes are located at a distal tip of said catheter assembly.

11. A method of intracellular delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes thereon at a treatment site;

causing said needle electrodes to penetrate in tissues of said treatment site;

introducing an agent through at least one of said needle electrodes to said treatment site; and

applying an electric field to said treatment site by said pair of needle electrodes to increase permeability of the cell membranes of the cells at said treatment site to allow said agent to pass through the cell membranes into the cells, wherein said electric field is a pulsed field of between 1 and approximately 100 pulses per second.

13. A method of intracellular delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes thereon at a treatment site;

causing said needle electrodes to penetrate in tissues of said treatment site;

introducing an agent through at least one of said needle electrodes to said treatment site; and

applying an electric field to said treatment site by said pair of needle electrodes to increase permeability of the cell membranes of the cells at said treatment site to allow said agent to pass through the cell membranes into the cells, wherein said electric field has a field strength of between approximately 10 V/cm and approximately 20 KV/cm.

14. A method of intracellular delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes thereon at a treatment site;

causing said needle electrodes to penetrate in tissues of said treatment site;

introducing an agent through at least one of said needle electrodes to said treatment site; and

applying an electric field to said treatment site by said pair of needle electrodes to increase permeability of the cell membranes of the cells at said treatment site to allow said agent to pass through the cell membranes into the cells, wherein said treatment site is an atherosclerotic lesion in a blood vessel.

15. A method of intracellular delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes thereon at a treatment site;

causing said needle electrodes to penetrate in tissues of said treatment site;

introducing an agent through at least one of said needle electrodes to said treatment site; and

applying an electric field to said treatment site by said pair of needle electrodes to increase permeability of the cell membranes of the cells at said treatment site to allow said agent to pass through the cell membranes into the cells, wherein the said treatment site is a restenotic lesion in a blood vessel.

16. A method of intracellular delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes thereon at a treatment site;

causing said needle electrodes to penetrate in tissues of said treatment site;

introducing an agent through at least one of said needle electrodes to said treatment site; and

applying an electric field to said treatment site by said pair of needle electrodes to increase permeability of the cell membranes of the cells at said treatment site to allow said agent to pass through the cell membranes into the cells, wherein the cells are smooth muscle cells.

17. A method of intracellular delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes thereon at a treatment site;

causing said needle electrodes to penetrate in tissues of said treatment site;

introducing an agent through at least one of said needle electrodes to said treatment site; and

applying an electric field to said treatment site by said pair of needle electrodes to increase permeability of the cell membranes of the cells at said treatment site to allow said agent to pass through the cell membranes into the cells, wherein said agent is selected from a group of extracellular matrix modulators, apoptosis inducers, anti-angiogenesis agents, matrix metalloproteinases (MMPs), and reperfusion injury inhibitors and combinations thereof.

18. A method of intracellular delivery of an agent, comprising:

positioning a catheter having a pair of needle electrodes thereon at a treatment site;

causing said needle electrodes to penetrate in tissues of said treatment site;

introducing an agent through at least one of said needle electrodes to said treatment site; and

applying an electric field to said treatment site by said pair of needle electrodes to increase permeability of the cell membranes of the cells at said treatment site to allow said agent to pass through the cell membranes into the cells, wherein said agent is selected from a group of nucleic acids, peptides and polypeptides.

19. An intraluminal apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen; and

a pair of needle electrodes integrated with said catheter assembly;

wherein said pair of needle electrodes are capable of being in electrical communication with a generator for applying an electric field to said treatment site, and wherein at least one needle electrode of said pair of needle electrodes allows for injection of an agent to said treatment site, and wherein said electric field has a field strength of between approximately 10 V/cm and approximately 20 KV/cm.

20. An intraluminal apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen; and

a pair of needle electrodes integrated with said catheter assembly;

wherein said pair of needle electrodes are capable of being in electrical communication with a generator for applying an electric field to said treatment site, and wherein at least one needle electrode of said pair of needle electrodes allows for injection of an agent to said treatment site, and wherein said apparatus is used for intracellular delivery of an agent to an atherosclerotic region of a blood vessel.

21. An intraluminal apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen; and

a pair of needle electrodes integrated with said catheter assembly;

wherein said pair of needle electrodes are capable of being in electrical communication with a generator for applying an electric field to said treatment site, and wherein at least one needle electrode of said pair of needle electrodes allows for injection of an agent to said treatment site, and wherein said apparatus is used for intracellular delivery of an agent to a restenotic region of a blood vessel.

22. An intraluminal apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen; and

a pair of needle electrodes integrated with said catheter assembly;

wherein said pair of needle electrodes are capable of being in electrical communication with a generator for applying an electric field to said treatment site, and wherein at least one needle electrode of said pair of needle electrodes allows for injection of an agent to said treatment site, and wherein said apparatus is used for intracellular delivery of an agent to a region of a mammalian heart.

23. An intraluminal apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen; and

a pair of needle electrodes integrated with said catheter assembly;

wherein said pair of needle electrodes are capable of being in electrical communication with a generator for applying an electric field to said treatment site, and wherein at least one needle electrode of said pair of needle electrodes allows for injection of an agent to said treatment site, and wherein said needle electrodes are retractable into said catheter.

24. An intraluminal apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen;

a pair of needle electrodes integrated with said catheter assembly, wherein said pair of needle electrodes are capable of being in electrical communication with a generator for applying an electric field to said treatment site, and wherein at least one needle electrode of said pair of needle electrodes allows for injection of an agent to said treatment site; and

a retractable sheath having an extended position and a retracted position, wherein when in said extended position said sheath covers said needle electrodes and when in said retracted position said needle electrodes are exposed.

25. An intraluminal apparatus for introducing an agent to a treatment site, comprising:

a catheter assembly for accessing a treatment site through an anatomical lumen; and

a plurality of needle electrodes integrated with said catheter assembly, said needle electrodes capable of being extended out from said catheter assembly to penetrate into tissue of said treatment site;

wherein said needle electrodes are configured to be in electrical communication with a generator for applying an electric field to said treatment site, and wherein at least one of said needle electrodes allows for injection of an agent to said treatment site, and wherein said needle electrodes are oriented about the circumference of said catheter assembly.