Multifunctional degradable nanoparticles with control over size and functionalities

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.

What is claimed is: 
     
         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 carboninc 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: 
       
         
           
           
               
               
           
         
       
       wherein Y is O, S, or N—R, wherein R is C1-C4 alkyl; 
       
         
           
           
               
               
           
         
       
       and 
       
         
           
           
               
               
           
         
       
       wherein L is a divalent alkyl chain or alkyloxyalkyl chain. 
     
     
         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:   
       
         
           
           
               
               
           
         
         
           wherein m is an integer from 0 to 6, and 
           wherein n is an integer from 0 to 2; or 
         
         (b) at least one propargyl-functionalized monomer residue having an optionally substituted structure represented by a formula: 
       
       
         
           
           
               
               
           
         
         
           wherein m 1  is an integer from 0 to 6, and 
           wherein n 1  is an integer from 0 to 2; or 
         
         (c) at least one monomer residue having an optionally substituted structure represented by a formula: 
       
       
         
           
           
               
               
           
         
         
           wherein n 2  is an integer from 0 to 2; or 
         
         (d) at least one keto-functionalized monomer residue having an optionally substituted structure represented by a formula: 
       
       
         
           
           
               
               
           
         
         
           wherein n 3  is an integer from 0 to 2.