MULTIFUNCTIONAL DEGRADABLE NANOPARTICLES WITH CONTROL OVER SIZE AND FUNCTIONALITIES

• US 20110274620A1
• Filed: 01/04/2010
• Published: 11/10/2011
• Est. Priority Date: 11/05/2007
• Status: Abandoned Application

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Calkins, David J., Harth, Eva M., Van Der Ende, Alice E.
• Application Number:
  US12/651,710
• Publication Number:
  US 20110274620A1
• Time in Patent Office: Days
• US Class Current: 424/9.1
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics

Abstract

In one aspect, the invention relates to polymers, crosslinked polymers, functionalized polymers, nanoparticles, and functionalized nanoparticles and methods of making and using same. In one aspect, the invention relates to degradable polymers and degradable nanoparticles. In one aspect, the invention relates to methods of preparing degradable nanoparticles and, more specifically, methods of controlling particle size during the preparation of degradable nanoparticles. In one aspect, the degradable nanoparticles are useful for complexing, delivering, and releasing payloads, including pharmaceutically active payloads. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Claims

1. A method of treating a ophthalmic disorder comprising administering to a subject an effective amount of a degradable polyester nanoparticle pharmaceutical or biologically active agent complex (nanoparticle complex).

2. The method of claim 1, wherein treating comprises inhibiting VEGF activity.

3. The method of claim 1, wherein treating comprises inhibiting carbonic anhydrase activity.

4. The method of claim 1, wherein the nanoparticle complex targets a cell in an ocular tissue.

5. The method of claim 4, wherein the tissue is selected from neuronal, fibrous, blood, gangloid, dermal, muscular, amacrine, bipolar, horizontal, connective, epithelial, and vitreal fluid.

6. The method of claim 5, wherein the tissue is from a region of the eye selected from sclera, cornea, retina, vitrius fluid, rods, cones, iris, zonular fibers, aqueous humour, choroid, ciliary muscle, optic disc, dura mater, optic nerve, fovea, and macula.

7. The method of claim 4, wherein the cell is a neuronal, epidermal, muscular, or gangloid cell.

8. The method of claim 1, wherein the ophthalmic disorder is selected from glaucoma, macular degeneration, keratoconus, Stargardt'"'"'s disease, scleritis, keratitis, corneal ulcer, and Thygeson'"'"'s superficial punctate keratopathy.

9. The method of claim 1, wherein the nanoparticle complex comprises one or more pharmaceutical or biologically active agents encapsulated by a degradable polyester nanoparticle.

10. The method of claim 9, wherein the pharmaceutical agent is a alpha agonist, beta blocker, prostaglandin analog, carbonic anhydrase inhibitor, or cholinergic.

11. The method of claim 10, wherein the pharmaceutical agent is selected from triamcinolone, ranibizumab, bevacizumab, pegaptanib (MACUGEN®

), travoprost, bimatoprost, methazolamide, brinzolamide, dorzolamide HCl, scetazolamide, memantine, timolol maleate, betaxolol HCl, levobunolol HCl, metipranolol, timolol hemihydrate, pilocarpine HCl, carbachol, brimonidine tartrate, apraclonidine HCl, and latanoprost (XALATAN®

).

12. The method of claim 9, wherein the nanoparticle complex comprises two or more pharmaceutical agents.

13. The method of claim 12, wherein the two pharmaceutical agents are dorzolomide HCl and timolol maleate or brimonidine tartrate and timolol maleate.

14. The method of claim 1, wherein the nanoparticle complex is administered to the subject via a route selected from ophthalmic, irrigation, topical, drops, epicutaneous, intravitreal, intraocular, conjunctival, subconjuctival, intracorneal, retrobulbar, intravenous, and intramuscular.

15. A composition comprising a degradable polyester nanoparticle and, encapsulated therein, a biologically active agent, a pharmaceutically active agent, or an imaging agent.

16. The composition of claim 15, wherein the biologically active agent is encapsulated within the nanoparticle.

17. The composition of claim 15, wherein the pharmaceutically active agent is encapsulated within the nanoparticle.

18. The composition of claim 15, wherein the imaging agent is encapsulated within the nanoparticle.

19. The composition of claim 15, wherein the degradable polyester nanoparticle comprises a crosslinked degradable nanoparticle having a polyester backbone and one or more crosslinks having a structure selected from:

20. The composition of claim 15, wherein the nanoparticle is produced by crosslinking a polymer comprising:

(a) at least one monomer residue having an optionally substituted structure represented by a formula;