Transdermal drug delivery by electroincorporation of vesicles

• US 5,464,386 A
• Filed: 09/22/1994
• Issued: 11/07/1995
• Est. Priority Date: 08/17/1992
• 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): Cohen, Lee S.
• Assistant Examiner(s): HUANG, STEPHEN D
• Application Number:
  US08/310,647
• Time in Patent Office: 411 Days
• Field of Search: 604/19, 604/20, 607/149, 607/150, 607/153, 428/402.2, 424/448, 424/449, 424/450
• US Class Current: 604/20
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61N 1/303 Constructional details electrodes for external use A61N1/0428
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

A method of transdermal molecular delivery comprises the steps of encapsulating molecules to be delivered in a vesicle, contacting a selected area of a tissue surface with a solution of the vesicles, and applying a pulsed electric field of sufficient amplitude to induce dielectric breakdown of the stratum corneum and to induce transport of the intact vesicle through the pores in the stratum corneum into the underlying tissue to enable diffusion of molecules into the tissue.

Claims

1. A method of molecular delivery through a surface tissue, comprising the steps of:

selecting a quantity of molecules to be delivered through the surface tissue;

selecting a quantity of vesicles as carriers;

encapsulating said molecules in said vesicles;

contacting a selected surface area of the surface tissue with a quantity of said vesicles; and

applying a pulsed electric field of sufficient amplitude and duration to induce pores in the surface tissue and to induce transport of said vesicles through said pores into a underlying tissue to enable diffusion of said molecules into the tissue.

2. A method according to claim 1 wherein said surface tissue is a stratum corneum and said electric field has a strength of from about 10 to about 60 kV/cm with a pulse length of from 10 usec to 10 msec.

3. A method according to claim 1 wherein selecting said vesicles to have a membrane and encapsulating the molecules within the membrane.

4. A method according to claim 1 wherein selecting said vesicles to be of a matrix construction and encapsulating the molecules within the matrix.

5. A method according to claim 1 wherein selecting said vesicles to have an electrical charge.

6. A method according to claim 1 wherein selecting said vesicles to be neutral.

7. A method according to claim 1 therein the step of applying the electric field includes applying a plurality of closely spaced electrodes to a surface area of a stratum corneum and applying pulses of from 10 to several hundred volts with a pulse length of between 100 usec to 100 msec.

8. A method according to claim 7 wherein selecting said vesicles to have a membrane and encapsulating the molecules within the membrane.

9. A method according to claim 8 wherein selecting said vesicles to have an electrical charge.

10. A method according to claim 8 wherein selecting said vesicles to be neutral.

11. A method according to claim 7 wherein selecting said vesicles to be of a matrix construction and encapsulating the molecules within the matrix.

12. A method according to claim 11 wherein selecting said vesicles to have an electrical charge.

13. A method according to claim 11 wherein selecting said vesicles to be neutral.

14. A method of transdermal delivery of molecules, comprising the steps of:

encapsulating molecules to be delivered in a vesicle;

contacting a selected area of stratum corneum surface with a quantity of the encapsulated molecules; and

applying a pulsed electric field of sufficient amplitude from about five volts to about six hundred volts and sufficient duration of from about one hundred usec to about one hundred msec to create open pores in said area of stratum corneum of sufficient size to receive vesicles and to induce passage of said vesicles through said stratum corneum into underlying tissue.

15. A method according to claim 14 wherein selecting said vesicles to have a membrane and encapsulating the molecules in the membrane.

16. A method according to claim 14 wherein forming said vesicles in the form of a matrix and encapsulating the molecules within the matrix.

20. A method according to claim 15 wherein selecting said vesicles to be neutral.

17. A method of transdermal delivery of molecules, comprising the steps of:

encapsulating molecules to be delivered in a matrix of a vesicle, wherein the vesicles are constructed to have a time release characteristic;

contacting a selected area of stratum corneum surface with a quantity of the encapsulated molecules; and

applying a pulsed electric field of sufficient amplitude from about five volts to about six hundred volts and sufficient duration of from about one hundred usec to about one hundred msec to create open pores in the area of stratum corneum of sufficient size to receive the vesicles and to induce passage of the vesicles through the stratum corneum into the tissue.

18. A method according to claim 17 wherein selecting said vesicles to have an electrical charge.

19. A method according to claim 17 wherein selecting said vesicles to have no electrical charge.