Thermoresponsive hydrogel containing polymer microparticles for noninvasive ocular drug delivery

1. A method for ocular delivery of an agent to a subject, comprising administering the agent at the lower fornix of an eye in the subject by topically delivering to an eye a liquid composition comprising agent-loaded polymer microparticles included in a hydrogel comprising poly(n-isopropyl acrylamide), and permitting the liquid composition to form in situ a gelled, sustained release film structure having a thickness of 10 μm to 1000 μm retained on the lower fornix of the eye, wherein the agent is sustainably released for a period of at least thirty days, and the liquid composition is in the form of an eye drop that can be self-administered by the subject.

2. The method of claim 1 , wherein the polymer microparticles comprise poly glycolide, poly lactic acid, poly (lactic-co-glycolic acid), alginate, polycaprolactone, cellulose, dextran, chitosan, or a combination thereof.

3. The method of claim 1 , wherein the agent-loaded polymer microparticles have a volume average diameter of 1 to 10 μm.

4. The method of claim 1 , wherein the agent is encapsulated in the polymer microparticles.

5. The method of claim 1 , wherein the agent is a therapeutic agent, and the method comprises administering a therapeutically effective amount of the therapeutic agent.

6. The method of claim 1 , wherein the agent is selected from an agent that lowers intraocular pressure, an antibiotic, an anti-inflammatory agent, a chemotherapeutic agent, an agent that promotes nerve regeneration, a steroid, or a combination thereof.

7. The method of claim 6 , wherein the agent is travoprost, bimatoprost, latanoprost, unoprostine, methazolamide, 5-acylimino- or related imino-substituted analog of methazolamide, timolol, levobunalol, carteolol, metipranolol, betaxolol, brimonidine, apraclonidine, pilocarpine, epinephrine, dipivefrin, carbachol, acetazolamide, dorzolamide, brinzolamide, or a pharmaceutically acceptable salt or ester thereof.

8. The method of claim 1 , wherein the method comprises treating an ocular condition in the subject.

9. The method of claim 8 , wherein the ocular condition is glaucoma, chronic dry eye, keratitis, post-operative inflammation, conjunctivitis, bacterial infection or fungal infection.

10. The method of claim 8 , wherein the ocular condition is glaucoma.

11. The method of claim 1 , wherein the agent is released in an amount from 1 to 10 μg per day for a period of time of at least five days.

12. The method of claim 1 , wherein the sustained delivery provides a rate of release that does not vary by more than 10% over a period of time of at least five days.

13. The method of claim 1 , wherein the sustained delivery provides a rate of release that does not vary by more than 20% over a period of time of at least five days.

14. The method of claim 1 , wherein the composition is administered at an interval of at least five days between administrations.

15. The method of claim 1 , wherein the hydrogel is biodegradable.

16. The method of claim 10 , wherein the active agent manages elevated intraocular pressure in the eye.

17. The method of claim 10 , wherein the active agent is brimonidine tartrate.

18. The method of claim 1 , wherein the agent-loaded polymer microparticles are suspended in the hydrogel.

19. The method of claim 1 , wherein the liquid composition is administered to the eye at an interval greater than at least one day between administrations.

20. The method of claim 1 , wherein the film structure has a thickness of 100 μm to 300 μm.

21. The method of claim 1 , wherein the film structure conforms to the shape of the lower fornix.

22. The method of claim 1 , wherein the liquid composition is delivered to the conjunctival cul-de-sac.

23. The method of claim 1 , wherein the film structure is opaque.

24. The method of claim 1 , wherein the film structure is passively retained on the lower fornix of the eye.