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 - 20 . (canceled) 
     
     
         21 . A method of preparing a nanoparticulate supramolecular complex comprising:
 contacting a therapeutic agent and a polymer to form a composite via a covalent bond, a non-covalent bond, a non-covalent interaction, or a combination thereof; and   covalently crosslinking the polymer of the composite under conditions sufficient to form a nanoparticulate supramolecular complex of a multi-dimensional polymer network containing the therapeutic agent.   
     
     
         22 . The method of  claim 21 , wherein the polymer is a cyclodextrin-containing polymer. 
     
     
         23 . The method of  claim 21 , wherein the polymer is a substantially linear polymer. 
     
     
         24 . The method of  claim 23 , wherein the substantially linear polymer is a substantially linear cyclodextrin-containing polymer. 
     
     
         25 . The method of  claim 24 , wherein the substantially linear cyclodextrin-containing polymer is a substantially linear cyclodextrin-containing copolymer having repeating units of formula Ia, Ib, or both: 
       
         
           
           
               
               
           
         
       
       wherein C is a substituted or unsubstituted cyclodextrin monomer and A is a comonomer bound to cyclodextrin C. 
     
     
         26 . The method of  claim 21 , wherein the polymer is a substantially branched polymer. 
     
     
         27 . The method of  claim 21 , wherein the polymer is a cationic polymer. 
     
     
         28 . The method of  claim 27 , wherein the cationic polymer is poly(ethylenimine). 
     
     
         29 . The method of  claim 28 , wherein the poly(ethylenimine) is substantially linear poly(ethylenimine). 
     
     
         30 . The method of  claim 28 , wherein the poly(ethylenimine) is substantially branched poly(ethylenimine). 
     
     
         31 . The method of  claim 21 , wherein the therapeutic agent and the polymer are contacted in solution. 
     
     
         32 . The method of  claim 21 , wherein the therapeutic agent is selected from an antibiotic, a steroid, a polynucleotide, a plasmid, a peptide, a peptide fragment, a small molecule, a chelating agent, a biologically active macromolecule, and a mixture thereof. 
     
     
         33 . The method of  claim 32 , wherein the therapeutic agent is a polynucleotide. 
     
     
         34 . The method of  claim 21 , further comprising contacting the composite or the supramolecular complex with a ligand to form a ligand-containing supramolecular complex, wherein the ligand allows the ligand-containing supramolecular complex to target or bind to a cell. 
     
     
         35 . The method of  claim 34 , wherein the ligand is selected from vitamins, proteins, and polysaccharides. 
     
     
         36 . The method of  claim 21 , wherein the crosslinking employs a crosslinking agent selected from adipic acid dihydrazide, polyethylene glycol 600 dihydrazide, dimethyl 3,3′-dithiobispropionimidate, dithiobis(succinimidyl propionate), disuccinimidyl suberate, and dimethylsuberimidate (DMS). 
     
     
         37 . The method of  claim 21 , wherein the supramolecular complex is prepared in a form suitable for administration to a patient. 
     
     
         38 . The method of  claim 21 , wherein the polymer is crosslinked with the same species of polymer. 
     
     
         39 . The method of  claim 21 , wherein the polymer is crosslinked with a different species of polymer. 
     
     
         40 . The method of  claim 21 , wherein the polymer comprises lysine moieties. 
     
     
         41 . A supramolecular complex prepared by a method of  claim 21 . 
     
     
         42 . A method of delivering a therapeutic agent comprising administering, to a patient in need thereof, a therapeutically effective amount of a supramolecular complex of  claim 41 . 
     
     
         43 . A supramolecular complex prepared by a method of  claim 23 . 
     
     
         44 . A method of delivering a therapeutic agent comprising administering, to a patient in need thereof, a therapeutically effective amount of a supramolecular complex of  claim 43 . 
     
     
         45 . A supramolecular complex prepared by a method of  claim 27 . 
     
     
         46 . A method of delivering a therapeutic agent comprising administering, to a patient in need thereof, a therapeutically effective amount of a supramolecular complex of  claim 45 . 
     
     
         47 . A method of preparing a supramolecular complex comprising:
 contacting a therapeutic agent and poly(ethylenimine) in solution to form a composite via a covalent bond, a non-covalent bond, a non-covalent interaction, or a combination thereof; and   covalently crosslinking the poly(ethylenimine) of the composite under conditions sufficient to form a supramolecular complex of a multi-dimensional polymer network containing the therapeutic agent.   
     
     
         48 . A method of preparing a supramolecular complex comprising:
 contacting a therapeutic agent and a linear polymer in solution to form a composite via a covalent bond, a non-covalent bond, a non-covalent interaction, or a combination thereof; and   covalently crosslinking the linear polymer of the composite under conditions sufficient to form a supramolecular complex of a multi-dimensional polymer network containing the therapeutic agent.   
     
     
         49 . A method of preparing a supramolecular complex comprising:
 contacting a therapeutic agent and a cyclodextrin-containing polymer in solution to form a composite via a covalent bond, a non-covalent bond, a non-covalent interaction, or a combination thereof; and   covalently crosslinking the cyclodextrin-containing polymer of the composite under conditions sufficient to form a supramolecular complex of a multi-dimensional polymer network containing the therapeutic agent.