Transmucosal drug delivery device and method including electrically-actuated permeation enhancement

• US 9,014,799 B2
• Filed: 10/08/2009
• Issued: 04/21/2015
• Est. Priority Date: 10/08/2009
• Status: Active Grant

• Current Assignee: Xerox Corporation (Xerox Holdings Corp.)
• Original Assignee: Palo Alto Research Center, Inc. (Xerox Holdings Corp.)
• Inventors: Uhland, Scott, Peeters, Eric, Wong, Serena
• Primary Examiner(s): Berdichevsky, Aarti B
• Assistant Examiner(s): SCHELL, LAURA C
• Application Number:
  US12/576,124
• Publication Number:
  US 20110087155A1
• Time in Patent Office: 2,021 Days
• Field of Search: 604/20, 604/891.1, 604/890.1, 604/48, 604/514, 604/515, 604/93.01, 604/285
• US Class Current: 604/20
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61N 1/0512 Anal electrodes
• CPC Class Codes: A61N 1/0524 Vaginal electrodes
• CPC Class Codes: A61N 1/18 Applying electric currents by contact electrodes
• 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

Intralumenal devices and methods are provided for transmucosal drug delivery. The device may comprise a housing configured for intralumenal deployment into a human or animal subject; a drug-dispensing portion which contains at least one drug; and an electrically-actuatable portion configured to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time while intralumenally deployed in the human or animal subject. The device may be operable to dispense the drug from the housing to a region of the mucosal barrier disrupted by the electrically-actuatable portion.

Claims

1. An intravaginal device for transmucosal drug delivery comprising:

a housing shaped and dimensioned for intravaginal deployment and for holding the device in place in the vagina by frictional engagement between the housing and mucosal tissue of a human or animal subject;

a drug-dispensing portion comprising a piston, an actuator, and a drug repository which contains at least one drug;

an electrically-actuatable portion comprising a plurality of electrically-actuatable active disruption elements configured to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time while intravaginally deployed and retained in the human or animal subject; and

a control module contained in the housing, the control module controlling the active disruption elements and the timing and sequence of the delivery of the drug from the drug repository by activation of the actuator and piston,

wherein the device is operable to dispense the drug from the housing to a region of the mucosal barrier disrupted by the electrically-actuatable portion.

2. The device of claim 1, wherein the drug comprises a protein or peptide.

3. The device of claim 1, wherein the drug comprises a hormone or steroid.

4. The device of claim 1, further comprising a receiver adapted to receive power or control signals from a transmitting device when the device is intralumenally deployed.

5. The device of claim 1, wherein the actuator comprises a mechanical displacement element, an osmotic swelling displacement element, a gas-volume displacement element, a magnetically-induced phase transformation element, a thermally-induced phase transformation element, a piezoelectric actuator, or an electrostatically-induced compression element.

6. The device of claim 1, wherein the electrically-actuatable active disruption elements are configured to disrupt the mucosal barrier by applying kinetic energy to the mucosal tissue.

7. The device of claim 1, wherein the electrically-actuatable active disruption elements are configured to disrupt the mucosal barrier by applying thermal energy or electromagnetic radiation to the mucosal tissue.

8. The device of claim 1, wherein the electrically-actuatable active disruption elements are configured to disrupt the mucosal barrier by applying electrical energy to the mucosal tissue.

9. The device of claim 1, wherein the electrically-actuatable active disruption elements are configured to disrupt the mucosal barrier by electroporation, electrothermal ablation, electrolysis, laser poration, laser ablation, jet penetration, jet cleaning, suction, acoustic disruption or a combination thereof.

10. The device of claim 1, wherein the electrically-actuatable active disruption elements are selected from the group consisting of a high velocity jet, a sound wave transducer, a laser, an electrode, a heating element, a vacuum nozzle, and a combination thereof.

11. A method for local transmucosal delivery of a drug to a human or animal subject comprising:

deploying and retaining a drug delivery device within a vagina of the human or animal subject, the device comprising a housing configured for holding the device in place in the vagina by frictional engagement with mucosal tissue and an electrically-actuatable portion;

actuating the electrically-actuatable portion to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time following the deployment; and

then after the mucosal barrier has been disrupted,

driving a piston in the housing to mechanically displace a drug from a reservoir in the housing, to thereby dispense the drug from the housing to a region of the disrupted mucosal barrier.

12. The method of claim 11, wherein the drug comprises a protein or peptide.

13. The method of claim 11, wherein the process of driving the piston comprises mechanical displacement, osmotic swelling displacement, gas-volume displacement, magnetically-induced phase transformation, thermally-induced phase transformation, piezoelectric actuation, or electrostatically-induced compression.

14. The method of claim 11, wherein the electrically-actuatable portion comprises one or more electrically-actuatable active disruption elements selected from the group consisting of a high velocity jet, a sound wave transducer, a laser, an electrode, a heating element, a vacuum nozzle, and a combination thereof.

15. The method of claim 11, wherein the step of actuating the electrically-actuatable portion comprise disrupting the mucosal barrier by electroporation, electrothermal ablation, electrolysis, laser poration, laser ablation, jet penetration, jet cleaning, suction, acoustic disruption or a combination thereof.

16. An intravaginal device for transmucosal drug delivery comprising:

a cylindrical housing configured for intravaginal deployment into and retention in a human or animal subject;

an electrically-actuatable portion comprising one or more electrically-actuatable active disruption elements configured to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time while deployed and retained in the vagina of the human or animal subject;

a drug dispenser comprising a drug repository containing at least one drug and a piston operable to dispense the at least one drug from the repository through a plurality of orifices or nozzles in the housing and in fluid communication with the repository into the region of the mucosal tissue disrupted by the electrically-actuatable portion; and

a control module contained in the housing, the control module controlling the active disruption elements and the timing and sequence of the delivery of the drug from the drug repository by activation of an acutator for the piston.

17. The device of claim 16, wherein the actuator comprises a mechanical displacement element, an osmotic swelling displacement element, a gas-volume displacement element, a magnetically-induced phase transformation element, a thermally-induced phase transformation element, or a combination thereof.

18. The device of claim 16, wherein the drug comprises a protein or peptide.

19. The device of claim 16, wherein the one or more electrically-actuatable active disruption elements are selected from the group consisting of a high velocity jet, a sound wave transducer, a laser, an electrode, a heating element, a vacuum nozzle, and a combination thereof.

20. The device of claim 16, wherein the electrically-actuatable active disruption elements are configured to disrupt the mucosal barrier by electroporation, electrothermal ablation, electrolysis, laser poration, laser ablation, jet penetration, jet cleaning, suction, acoustic disruption, or a combination thereof.

21. The device of claim 16, wherein the electrically-actuatable portion and the drug dispenser are cooperatively configured to administer the at least one drug after the disruption of the mucosal tissue barrier.

22. An intravaginal device for transmucosal drug delivery comprising:

a cylindrical housing shaped and dimensioned for intravaginal deployment and for holding the device in place in the vagina by frictional engagement between the housing and mucosal tissue of a human or animal subject, the housing having a plurality of dispensing nozzles;

an electrically-actuatable portion comprising one or more electrically-actuatable active disruption elements configured to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time while deployed and retained in the vagina of the human or animal subject, and

a drug dispenser comprising

a drug repository containing at least one drug, the drug repository being located in the axial center of the housing in fluid communication with the plurality of dispensing nozzles, and

a positive displacement element adapted to apply a mechanical force to the at least one drug to dispense the at least one drug from the plurality of dispensing nozzles into the region of the mucosal tissue disrupted by the electrically-actuatable portion.

23. The intravaginal device of claim 22, wherein the plurality of nozzles dispense the drug radially in at least two opposed directions from a sidewall of the cylindrical housing.

24. The intravaginal device of claim 22, wherein the positive displacement element comprises a piston and an actuator operably associated with the piston.