Methods and devices for drug delivery to ocular tissue using microneedle

• US 8,197,435 B2
• Filed: 04/26/2010
• Issued: 06/12/2012
• Est. Priority Date: 05/02/2006
• Status: Active Grant

• Current Assignee: Emory University, Georgia Tech Research Corporation (University System of Georgia)
• Original Assignee: Emory University, Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Prausnitz, Mark R., Edelhauser, Henry F., Patel, Samirkumar Rajnikant
• Primary Examiner(s): Lucchesi, Nicholas
• Assistant Examiner(s): PATEL, PRITESH ASHOK
• Application Number:
  US12/767,768
• Publication Number:
  US 20100256597A1
• Time in Patent Office: 778 Days
• Field of Search: 604/19
• US Class Current: 604/19
• CPC Class Codes: A61F 9/0008 Introducing ophthalmic products into the ocular cavity or retaining products therein putting in contact lenses A61F9/0061; introducing or retaining media in cavities of the body in general A61M31/00
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2210/0612 Eyes
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics

Abstract

Methods and devices are provided for targeted administration of a drug to a patient'"'"'s eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Claims

1. A method of administering a drug to an eye of a patient, comprising:

inserting a hollow microneedle into the sclera of the eye at an insertion site, the microneedle having a tip end with an opening; and

infusing over a period of time a fluid drug formulation, which comprises a drug, through the inserted microneedle and into the suprachoroidal space of the eye,

wherein during the period the infused drug formulation flows within the suprachoroidal space away from the insertion site.

2. The method of claim 1, wherein during the period the infused fluid drug formulation flows at least 5 mm away from the insertion site.

3. The method of claim 1, wherein the insertion site is at about the equator of the eye.

4. The method of claim 1, wherein the insertion site is between the equator and the limbus of the eye.

5. The method of claim 4, wherein at least a portion of the fluid drug formulation reaches ocular tissue posterior to the equator of the eye during the period.

6. The method of claim 1, wherein the microneedle is inserted into the surface of the sclera at an angle of about 90 degrees.

7. The method of claim 1, wherein the tip end of the microneedle is inserted substantially to the base of the sclera without completely penetrating through the sclera.

8. The method of claim 1, wherein the tip end of the microneedle is inserted through the sclera into the suprachoroidal space without penetrating through the choroid.

9. The method of claim 1, further comprising using imaged-guided feedback to determine the location of the microneedle in the eye and/or the location of infused fluid drug formulation within the eye.

10. The method of claim 1, wherein from about 10 μ

L to about 200 μ

L of the fluid drug formulation is infused.

11. The method of claim 1, wherein the fluid drug formulation comprises a suspension of microparticles or nanoparticles, the microparticles or nanoparticles comprising the drug.

12. The method of claim 11, wherein the suspension further comprises a physiologically acceptable aqueous vehicle.

13. The method of claim 1, wherein the fluid drug formulation comprises a formulation that undergoes a phase change after being infused into the suprachoroidal space.

14. The method of claim 1, wherein the step of infusing comprises driving the fluid drug formulation at an infusion pressure of at least 150 kPa.

15. The method of claim 1, wherein the step of infusing comprises driving the fluid drug formulation at an infusion pressure of at least 300 kPa.

16. The method of claim 1, wherein the microneedle has an effective length between 500 microns and 1000 microns.

17. The method of claim 1, wherein the microneedle has an effective length between 700 microns and 1000 microns.

18. The method of claim 1, wherein the microneedle has an effective length between 800 microns and 1000 microns.

19. The method of claim 1, wherein the portion of the microneedle that is inserted into the sclera has a maximum cross-sectional width or diameter of 400 microns.

20. The method of claim 1, wherein the microneedle is formed of metal and has a total effective length between 500 microns and 1000 microns, the microneedle comprising a cylindrical shaft having an outer diameter of between 200 microns and 400 microns, and a beveled tip less than about 400 microns in length.

21. The method of claim 1, wherein the microneedle extends substantially perpendicularly from a planar or convex base.

22. The method of claim 1, wherein the patient is in need of treatment of uveitis, glaucoma, diabetic macular edema, wet or dry age-related macular degeneration, choroidal neovascularization, or cytomegalovirus retinitis.

23. A method of administering a drug to an eye of a patient, comprising:

(a) inserting a hollow microneedle into the sclera of the eye at an insertion site, the microneedle having a tip end with an opening;

(b) applying a selected pressure to a fluid drug formulation, which comprises a drug, to induce infusion of the drug formulation through the inserted microneedle;

(c) determining whether the drug formulation has flowed into the suprachoroidal space of the eye and away from the insertion site;

(d) if the determination in step (c) is that the drug formulation has flowed into the suprachoroidal space away from the insertion site, then infusing a selected volume of the fluid drug formulation and thereupon removing the pressure, or if the determination in step (c) is that substantially none of the drug formulation has flowed into the suprachoroidal space away from the insertion site, then repositioning the inserted microneedle and repeating steps (b)-(d) until a selected volume of the fluid drug formulation has been infused; and

(e) retracting the microneedle from the eye.

24. A device for administration of a drug to the eye of a patient, comprising:

a hollow microneedle having a tip end and a bore through which a fluid can be communicated through the microneedle;

a device body for holding the microneedle, the device body having an end serving as a base from which the microneedle extends; and

an actuator for controlled infusion of a fluid drug formulation through the microneedle,

wherein the device is configured for insertion of the tip of the microneedle into an insertion site in the sclera of the eye and the device is operable to infuse the fluid drug formulation into the suprachoroidal space and away from the insertion site.

25. The device of claim 24, wherein the device is operable to provide controlled infusion of from 10 μ

L to 200 μ

L of the fluid drug formulation.

26. The device of claim 24, wherein the device is operable to infuse the fluid drug formulation at a pressure of at least 150 kPa.

27. The device of claim 24, further comprising a fluid reservoir for containing the fluid drug formulation, the fluid reservoir being in operable communication with the bore of the microneedle at the base.

28. The device of claim 27, wherein the fluid reservoir comprises the fluid drug formulation.

29. The device of claim 24, wherein the microneedle has an effective length between 500 microns and 1000 microns.

30. The device of claim 29, wherein the microneedle has a maximum cross-sectional width or diameter of about 400 microns.