TRANSMUCOSAL DRUG DELIVERY DEVICE AND METHOD INCLUDING CHEMICAL PERMEATION ENHANCERS

• US 20110087192A1
• Filed: 10/08/2009
• Published: 04/14/2011
• 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: Fatakdawala, Hussain, Peeters, Eric, Uhland, Scott
• Granted Patent: US 8,882,748 B2
• Time in Patent Office: Days
• US Class Current: 604/514
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61M 2210/1475 Vagina
• 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

Abstract

Devices and methods are provided for transmucosal drug delivery. The transmucosal drug delivery device may include a housing configured for intralumenal deployment, such as intravaginally, into a human or animal subject; a drug-dispensing portion which contains at least one drug, the drug-dispensing portion being configured to dispense the drug from the housing by positive displacement; and a permeability enhancer-dispensing portion configured to release or generate a permeability enhancing substance 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 permeability enhancing substance.

Claims

1. An intralumenal device for transmucosal drug delivery comprising:

a housing configured for intralumenal deployment into a human or animal subject;

a drug-dispensing portion which contains at least one drug, the drug-dispensing portion being configured to dispense the drug from the housing by positive displacement; and

a permeability enhancer-dispensing portion configured to release or generate a permeability enhancing substance 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,

wherein the device is operable to dispense the drug from the housing to a region of the mucosal barrier disrupted by the permeability enhancing substance.

2. The device of claim 1, wherein the device is configured to generate the permeation enhancing substance in vivo.

3. The device of claim 1, wherein the permeation enhancing-dispensing portion comprises an electrochemical element.

4. The device of claim 1, wherein the permeation enhancing substance comprises hydrogen peroxide.

5. The device of claim 1, wherein the housing is configured for intravaginal deployment.

6. The device of claim 1, wherein the permeability enhancing substance is stored in a first repository and the drug is stored in a second repository separate from the permeability enhancing substance.

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

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

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

10. The device of claim 1, further comprising a controller configured to sequence the operations of the drug-dispensing portion and permeability-enhancer dispensing portion.

11. The device of claim 1, wherein the drug dispensing portion comprises a positive displacement element for actively dispensing the drug from the housing selected from the group consisting of 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, an electrostatically-induced compression element, an actuatable dispensing valve with a static pressure head and a combination thereof.

12. The device of claim 1, wherein the permeability enhancing substance comprises a chemical enhancer selected from the group consisting of DMSO, hydrogen peroxide, propylene glycol, oleic acid, cetyl alcohol, benzalkonium chloride, sodium lauryl sulphate, isopropyl myristate, Tween 80, dimethyl sulfoxide, dimethyl formamide, dimethyl acetamide, sodium lauroylsarcosinate, sorbitan monolaurate, methylsulfonylmethane, Azone, terpenes, phosphatidylcholine dependent phospholipase C, triacyl glycerol hydrolase, acid phosphatase, phospholipase A2, a concentrated saline solution, and a combination thereof.

13. The device of claim 1, wherein the permeability enhancing substance comprises an enzyme inhibitor selected from the group consisting of protease inhibitors, antiretrovirals, diisopropylfluorophosphate (DFP), α

-difluoromethylornithine (DFMO), trypanothione reductase, methotrexate, allopurinol, acyclovir, and a combination thereof.

14. The device of claim 1, wherein the permeability enhancer-dispensing portion comprises a positive displacement element for actively dispensing the drug from the housing selected from the group consisting of 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, an electrostatically-induced compression element, an actuatable dispensing valve with a static pressure head and a combination thereof.

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

deploying a drug delivery device within a mucosal tissue lumen;

releasing from, or generating with, the device a permeability enhancing substance such that the permeability enhancing substance contacts a region of the mucosal tissue; and

dispensing from the drug delivery device a drug by a positive displacement process such that the drug is delivered to the region of the mucosal tissue that is contacted by the permeability enhancing substance.

16. The method of claim 15, wherein the drug delivery device is deployed within the vagina, uterus, or rectum of the human or animal subject.

17. The method of claim 15, wherein the drug comprises a protein or peptide.

18. The method of claim 15, wherein the positive displacement process comprises mechanical displacement, osmotic swelling displacement, gas-volume displacement, magnetically-induced phase transformation, thermally-induced phase transformation, piezoelectric actuation, electrostatically-induced compression, static pressure head displacement through an actuatable dispensing valve, or a combination thereof.

19. The method of claim 15, wherein the permeation enhancing substance comprises hydrogen peroxide.

20. The method of claim 15, wherein the permeability enhancing substance comprises a chemical enhancer selected from the group consisting of DMSO, propylene glycol, oleic acid, cetyl alcohol, benzalkonium chloride, sodium lauryl sulphate, isopropyl myristate, Tween 80, dimethyl sulfoxide, dimethyl formamide, dimethyl acetamide, sodium lauroylsarcosinate, sorbitan monolaurate, methylsulfonylmethane, Azone, terpenes, phosphatidylcholine dependent phospholipase C, triacyl glycerol hydrolase, acid phosphatase, phospholipase A2, a concentrated saline solution, and a combination thereof.

21. The method of claim 15, wherein the permeability enhancing substance comprises an enzyme inhibitor selected from the group consisting of protease inhibitors, antiretrovirals, diisopropylfluorophosphate (DFP), α

-difluoromethylornithine (DFMO), trypanothione reductase, methotrexate, allopurinol, acyclovir, and a combination thereof.

26. The device of claim 21, wherein the drug comprises a protein or peptide.

22. An intravaginal device for transmucosal drug delivery comprising:

a housing configured for intravaginal deployment into a human or animal subject;

a drug dispenser containing a drug, the drug dispenser having one or more nozzles and a positive displacement element adapted to dispense the drug from the housing through the one or more nozzles by positive displacement; and

a permeability enhancer dispenser configured to release or generate a permeability enhancing substance to disrupt at least one region of a mucosal barrier adjacent to the housing at a selected time while intravaginally deployed in the human or animal subject,

wherein the device is operable to dispense the drug from the housing to a region of the mucosal barrier disrupted by the permeability enhancing substance.

23. The device of claim 22, wherein the permeation enhancer dispenser comprises one or more electrochemical elements configured to generate hydrogen peroxide in vivo.

24. The device of claim 22, further comprising a controller configured to control the actuation of the positive displacement element and the permeability enhancer dispenser.

25. The device of claim 22, wherein the positive displacement element is selected from the group consisting of 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, and a combination thereof.

27. A medical device comprising:

a housing configured for intralumenal deployment into a human or animal subject; and

a permeability enhancer-dispensing portion configured to release or generate hydrogen peroxide 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.