POLYMERIC DRUG CONJUGATES WITH TETHER GROUPS FOR CONTROLLED DRUG DELIVERY
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)