Method of preparing a supramolecular complex containing a therapeutic agent and a multi-dimensional polymer network

Abstract

A method of preparing a supramolecular complex containing at least one therapeutic agent and a multi-dimensional polymer network is described. A supramolecular complex prepared by a method of the invention is described. A method of treatment by administering a therapeutically effective amount of a supramolecular complex of the invention is also described. Such a supramolecular complex may be used as a delivery vehicle for various therapeutic agents.

1 . A method of preparing a supramolecular complex comprising the steps of:
 contacting at least one therapeutic agent and at least one polymer to form a composite, and   treating said polymer of said composite under conditions sufficient to form a supramolecular complex comprising said therapeutic agent and a multi-dimensional polymer network.   
     
     
         2 . The method of  claim 1 , wherein said polymer of said composite is a substantially linear polymer, a substantially branched polymer, or a mixture thereof. 
     
     
         3 . The method of  claim 2 , wherein said substantially linear polymer is linear polyethyleneimine or a linear cyclodextrin-containing polymer and said substantially branched polymer is branched polyethyleneimine or a branched cyclodextrin-containing polymer. 
     
     
         4 . The method of  claim 3 , wherein said linear cyclodextrin-containing polymer is a linear cyclodextrin copolymer or a linear oxidized cyclodextrin copolymer and said branched cyclodextrin-containing polymer is a branched cyclodextrin copolymer or a branched oxidized cyclodextrin copolymer. 
     
     
         5 . The method of  claim 1 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, a plasmid, a peptide, a peptide fragment, a small molecule, a chelating agent and a biologically active macromolecule. 
     
     
         6 . The method of  claim 5 , wherein said therapeutic agent is DNA. 
     
     
         7 . The method of  claim 5 , wherein said therapeutic agent is modified with at least one ligand. 
     
     
         8 . The method of  claim 7 , wherein said ligand is selected from the group consisting of vitamins, proteins, and polysaccharides. 
     
     
         9 . The method of  claim 1 , wherein said treating step comprises the addition of at least one crosslinking agent. 
     
     
         10 . The method of  claim 9 , wherein said crosslinking agent is selected from the group consisting of adipic acid dihydrazide, polyethylene glycol 600 dihydrazide, dimethyl 3,3′-dithiobispropionimidate, dithiobis(succinimidyl propionate), disuccinimidyl suberate, and dimethylsuberimidate (DMS). 
     
     
         11 . The method of  claim 1 , further comprising the step of contacting said composite with at least one ligand to form a ligand-containing composite. 
     
     
         12 . The method of  claim 11 , wherein said ligand is selected from the group consisting of vitamins, proteins, and polysaccharides. 
     
     
         13 . The method of  claim 1 , further comprising the step of contacting said supramolecular complex with at least one ligand to form a ligand-containing supramolecular complex. 
     
     
         14 . The method of  claim 13 , wherein said ligand is selected from the group consisting of vitamins, proteins, and polysaccharides. 
     
     
         15 . A supramolecular complex comprising:
 a composite comprising at least one therapeutic agent and a polymer; and a multi-dimensional polymer network.   
     
     
         16 . A method of treating a subject, the method comprising the step of administering a therapeutically effective amount of a supramolecular complex, wherein the supramolecular complex comprises: a composite comprising at least one therapeutic agent and a polymer; and a multi-dimensional polymer network. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . The supramolecular complex of  claim 15  comprising a plurality of therapeutic agents. 
     
     
         20 . A method of delivering a therapeutic agent to a subject, the method comprising the step of administering to the subject a therapeutically effective amount of a supramolecular complex, wherein the supramolecular complex comprises: a composite comprising at least one therapeutic agent and a polymer; and a multi-dimensional polymer network. 
     
     
         21 . The method of  claim 16 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, a plasmid, a peptide, a peptide fragment, a small molecule, a chelating agent and a biologically active macromolecule. 
     
     
         22 . The supramolecular complex of  claim 19 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, a plasmid, a peptide, a peptide fragment, a small molecule, a chelating agent and a biologically active macromolecule. 
     
     
         23 . The method of  claim 20 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, a plasmid, a peptide, a peptide fragment, a small molecule, a chelating agent and a biologically active macromolecule. 
     
     
         24 . The method of  claim 16 , wherein said polymer of said composite is a substantially linear polymer, a substantially branched polymer, or a mixture thereof. 
     
     
         25 . The supramolecular complex of  claim 15 , wherein said polymer of said composite is a substantially linear polymer, a substantially branched polymer, or a mixture thereof. 
     
     
         26 . The method of  claim 20 , wherein said polymer of said composite is a substantially linear polymer, a substantially branched polymer, or a mixture thereof.