Polymeric drug conjugates with tether groups for controlled drug delivery

Abstract

Described herein is a cyclodextrin containing polymer conjugate.

1 . A linear, cyclodextrin containing polymer conjugate, comprising a therapeutic agent covalently attached to a polymer through a tether, wherein the tether comprises a self-cyclizing moiety. 
     
     
         2 . The polymer conjugate of  claim 1 , wherein the tether further comprises a selectivity-determining moiety. 
     
     
         3 . The polymer conjugate of  claim 2 , wherein the selectivity-determining moiety is attached via a bond to the self-cyclizing moiety between the self-cyclizing moiety and the polymer. 
     
     
         4 . The polymer conjugate of  claim 3 , wherein the bond between the selectivity-determining moiety and the self-cyclizing moiety is selected from the group consisting of an amide, a carbamate, a carbonate, an ester, a thioester, a urea, and a disulfide bond. 
     
     
         5 . The polymer conjugate of  claim 3 , wherein the bond between the selectivity-determining moiety and the self-cyclizing moiety is an ester bond. 
     
     
         6 . The polymer conjugate of  claim 3 , wherein cleavage of the bond between the selectivity-determining moiety and the self-cyclizing moiety results in cyclization of the self-cyclizing moiety, thereby releasing the therapeutic agent from the polymer. 
     
     
         7 . The polymer conjugate of  claim 6 , wherein cyclization of the self-cyclizing moiety forms a five- or six-membered ring. 
     
     
         8 . The polymer conjugate of  claim 7 , wherein the five- or six-membered ring is a heterocycle comprising at least one heteroatom selected from the group consisting of a nitrogen, an oxygen, and a sulfur. 
     
     
         9 . The polymer conjugate of  claim 6 , wherein the cyclization of the self-cyclizing moiety forms a five-membered ring. 
     
     
         10 . The polymer conjugate of  claim 9 , wherein the five-membered ring comprises two heteroatoms selected from the group consisting of a nitrogen, an oxygen, and a sulfur. 
     
     
         11 . The polymer conjugate of  claim 9 , wherein the five-membered ring comprises two oxygen atoms. 
     
     
         12 . The polymer conjugate of  claim 1 , wherein the cyclodextrin containing polymer comprises a copolymer comprising cyclodextrin moieties and linker groups that do not comprise cyclodextrin moieties. 
     
     
         13 . The polymer conjugate of  claim 12 , wherein the cyclodextrin moieties and the linker groups alternate in the copolymer. 
     
     
         14 . The polymer conjugate of  claim 12 , wherein each linker group independently comprises an alkyl chain, a polyethylene glycol (PEG) chain, polysuccinic anhydride, poly-L-glutamic acid, poly(ethyleneimine), an oligosaccharide, or an amino acid chain. 
     
     
         15 . The polymer conjugate of  claim 12 , wherein each linker group comprises PEG. 
     
     
         16 . The polymer conjugate of  claim 1 , wherein the cyclodextrin is alpha-, beta-, or gamma-cyclodextrin, e.g., beta-cyclodextrin. 
     
     
         17 . The polymer conjugate of  claim 1 , wherein the therapeutic agent is a small molecule, a peptide, a protein, a nucleotide, a polynucleotide, or a polymer that has therapeutic function. 
     
     
         18 . The polymer conjugate of  claim 1 , wherein the therapeutic agent is an anti-cancer, anti-fungal, anti-bacterial, anti-mycotic, or anti-viral therapeutic. 
     
     
         19 . The polymer conjugate of  claim 1 , wherein the therapeutic agent is a protease inhibitor. 
     
     
         20 . The polymer conjugate of  claim 1 , wherein the therapeutic agent comprises an amino, hydroxyl, or thiol group. 
     
     
         21 - 31 . (canceled)