Control of transport of molecules across tissue using electroporation

• US 5,019,034 A
• Filed: 03/30/1989
• Issued: 05/28/1991
• Est. Priority Date: 01/21/1988
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Powell, Kevin T., Weaver, James C., Langer, Robert S. Jr.
• Primary Examiner(s): Pellegrino, Stephen C.
• Assistant Examiner(s): Lewis, Ralph A.
• Application Number:
  US07/331,263
• Time in Patent Office: 789 Days
• Field of Search: 604/890.1, 604/20, 128/798, 128/802
• US Class Current: 604/20
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• 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

An electrical process for enhancing and/or controlling transport of molecules across tissue such as human and animal skin is disclosed. The process involves the use of a high voltage, short duration electrical pulses on the tissue surface to produce electroporation. Once this effect has occurred, concentration, pressure or temperature gradients, or iontopheresis can be used to move molecules across the tissue. The process can be repeatedly applied without producing undesirable tissue damage or can be used to purposely cause highly limited tissue damage for the purpose of providing a desired, relatively long term molecular transport pathway. The occurrence of the electroporation effect can be detected by monitoring the tissue for a reversible electrical breakdown, which, along with an enhanced tissue permeability, is the characteristic effect of electroporation.

Claims

1. A method for transporting molecules across tissue comprising the steps of:

a. applying at least one electrical pulse of sufficient voltage and duration to a region of tissue, wherein the tissue comprises at least a single layer of cells, in order to cause electroporation in the region; and

b. utilizing a driving force to move molecules across the regions of the tissue undergoing electroporation.

2. A method of claim 1, wherein the tissue is selected from the group consisting of animal tissue and plant tissue.

3. A method as in claim 2, wherein the animal tissue comprises skin.

4. A method as in claim 3, wherein the skin comprises human skin.

5. A method as in claim 2, wherein the animal tissue is selected from the group consisting of buccal, vaginal and rectal membrane.

6. A method as in claim 2, wherein the tissue is artificial tissue.

7. A method as in claim 2, wherein a high permeability state caused by the electroporation is used to increase and control molecular transport through the walls of sweat ducts or hair follicles.

8. A method as in claim 1, wherein the driving force is electrical force.

9. A method as in claim 8, wherein the driving force is iontopheresis.

10. A method as in claim 1, wherein the driving force is a non-electrical physical or chemical force.

11. A method as in claim 10, wherein the driving physical force is selected from the group consisting of:

pressure gradients, and concentration gradients.

12. A method as in claim 1, wherein the transported molecules comprise a pharmaceutical.

13. A method as in claim 1, wherein the transported molecules comprise a compound of diagnostic interest.

14. A method as in claim 1, further comprising the step of monitoring the electrical resistance of the tissue in order to determine the occurrence of reversible electrical breakdown.

15. A method as in claim 14, wherein the measurement of the reversible electrical breakdown is used to provide an indication of the occurrence of electroporation.

16. A method as in claim 15, wherein the measurement of reversible electrical breakdown is used to provide an indication of the occurrence of electroporation to a means capable of automatically controlling pulse voltage and duration as well as time between pulses when more than one pulse is applied.

17. A method as in claim 14, wherein electrical resistance of the tissue is determined from the reversible electrical breakdown measurement, said electrical resistance being used to estimate the change in the permeability of the tissue.

18. A method as in claim 1, wherein the electrical pulse is of sufficient voltage and duration to produce a permanent, high permeability condition in some cells of the tissue undergoing electroporation.

19. A method as in claim 18 in which the electrical resistance of the tissue is monitored in order to determine the occurrence of a permanent high permeability condition is some cells of the tissue undergoing electroporation.

20. A method as in claim 1, wherein the electrical pulse is selected from the group consisting of square wave pulses, saw tooth pulses, triangular wave pulses, exponential wave pulses and sine wave pulses.

21. A method for temporarily increasing the permeability of tissue which comprises applying at least one electrical pulse of sufficient voltage and duration to a region of tissue, wherein the tissue comprises at least a single layer of cells, said method further characterized by the occurrence of reversible electrical breakdown in the electroporated region and wherein the electroporated region is used as a site of molecular transport.

22. A method as in claim 21, wherein a driving force is used to increase molecular transport at the electroporated region.

23. A method as in claim 22, wherein the driving force is selected form the group consisting of pressure gradients, concentration gradients, and iontophoresis.