Oxazoline Polymer Compositions and Use Thereof

Abstract

Compositions comprising an oxazoline polymer and optional linkers to carry a variety of molecules.

We claim: 
     
         1 . A functionalized polyoxazoline polymer, wherein said polymer comprises the formula:
   I n -P-L-M-B, wherein   I is an initiator,   n≧1,   P is a polyoxazoline polymer,   L is a first linker comprising at least two amine groups, at least two imino (—NH—) groups or at least an amino group and an imino group, wherein said first linker is attached to said polymer by one of said at least two amine groups, at least two imino (—NH—) groups or at least an amino group and an imino group,   M is a second linker and   B is a bioactive material.   
     
     
         2 . The polymer of  claim 1 , wherein said initiator comprises an alkyl, an aryl, an ester, an amide or a sulfur-containing compound. 
     
     
         3 . The polymer of  claim 1 , wherein said initiator comprises a bioactive material. 
     
     
         4 . The polymer of  claim 3 , wherein said bioactive material comprises a member of a binding pair (BP), a biologically active molecule (BAM), or a pharmaceutically active agent (PAA). 
     
     
         5 . The polymer of  claim 4 , wherein said PAA is a small molecule drug or a large molecule drug. 
     
     
         6 . The polymer of  claim 5 , wherein said large molecule drug comprises a polypeptide or a polynucleotide. 
     
     
         7 . The polymer of  claim 1 , wherein said polymer comprise a poly (unsubstituted oxazoline) or a poly(substituted oxazoline) 
     
     
         8 . The polymer of  claim 7 , wherein said poly(substituted oxazoline) comprises a poly (2-methyloxazoline), a poly (2-ethyloxazoline), a poly (2-propyloxazoline), a poly (2-butyloxazoline) or a combination thereof. 
     
     
         9 . The polymer of  claim 1 , wherein said P comprises a linear, a star branched, a combbranched, a dendrimer, a dendrigraft, a hyperbranched, a randomly branched polyoxazoline polymer, or a combination thereof. 
     
     
         10 . The polymer of  claim 1 , wherein said second linker M comprises a linear, a dendritic polymer, a randomly branched polymer, or a combination thereof. 
     
     
         11 . The polymer of  claim 5 , wherein said small molecule drug comprises a paclitaxel, a gemcitabine, a camptothecin, or a combination thereof. 
     
     
         12 . The polymer of  claim 1 , wherein said small molecule comprises an entire or a portion of ammonia, ethylenediamine, piperazine, cyclen, tren, 4-(aminomethyl)piperidine, 1,3-diaminopropane, 2,2′-(ethylenedioxy)bis(ethylamine), 1,11 -diamino-3,6,9-trioxaundecane, diethylenetriamine, hexamethylenediamine, triethylenetetramine or tris(2-aminoethyl)amine, 1,8-diaminooctane. 
     
     
         13 . The polymer of  claim 1 , wherein said first linker L is reacted with or modified by carbodiimide (CDI), a CDI-functionalized molecule, glycidol, succinic anhydride, acrylic ester, amidoamine, linear or branched polyamidoamine, acrylamide or an N-hydroxysuccinimide (NHS)-containing heterofunctional molecule. 
     
     
         14 . The polymer of  claim 13 , wherein said heterofunctional molecule comprises an end which is activated with N-hydroxysuccinimide (NHS) or an aldehyde functional group. 
     
     
         15 . The polymer of  claim 1 , wherein B is linked to M through a hydrolytically stable or unstable linkage. 
     
     
         16 . The polymer of  claim 1 , wherein B is physically mixed with said polymer modified with said linker or linkers. 
     
     
         17 . The polymer of  claim 1 , where said initiator comprises ethyl bromoacetate, methyl bromoacetate, tert-butyl bromoacetate, propyl bromoacetate, benzyl bromoacetate, a sulfur-containing compound, a silicon-containing compound or a protected amine or imine. 
     
     
         18 . The polymer of  claim 17 , wherein said sulfur-containing compound is 2-(p-toluenesulfonyloxy)ethyl disulfide (TOEDS), (chloromethyl) methyl disulfide or bis(iodomethyl)methyl disulfide, 2-bromoethyl disulfide, 
     
     
         19 . The polymer of  claim 17 , wherein said silicon-containing compound is (3-chloropropyl)triethoxysilane, (3-bromopropyl)trimethoxysilane or (3-iodopropyl)trimethoxysilane. 
     
     
         20 . The polymer of  claim 17 , wherein protected amine or imine is protected with a carboxybenzyl, a p-methoxybenzyl carbonyl, a tert-butyloxycarbonyl or a 9-fluorenylmethyloxycarbonyl (FMOC) group. 
     
     
         21 . The polymer of  claim 3 , where said bioactive material on said initiator or B comprises a targeting moiety. 
     
     
         22 . The polymer of  claim 21 , wherein said targeting moiety comprises an antibody or an antigen-binding portion thereof. 
     
     
         23 . The polymer of  claim 21 , wherein the other bioactive material comprises a PAA. 
     
     
         24 . A composition comprising the polymer of  claim 4  and a detectable reporter.