Anti-cancer agent delivery vehicles capable of improved loading

Abstract

There is provided a conjugate of a delivery agent containing a chemical moiety and at least one flavonoid. The flavonoid exists in a monomeric form or dimeric form before conjugation and remains in the monomeric form or dimeric form after conjugation. Preferably, the conjugate comprises two flavonoids. The delivery agent is conjugated at the C6 and/or the C8 position of the A ring of the flavonoid. An anti-cancer agent delivery vehicle comprising an anti-cancer agent and the conjugate is also provided.

1 .- 24 . (canceled) 
     
     
         25 . A method of conjugating a delivery agent containing a chemical moiety to at least one flavonoid, the method comprising reacting the delivery agent with the flavonoid, wherein the flavonoid exists in a monomeric form or dimeric form before conjugation and remains in the monomeric form or dimeric form after conjugation; wherein the chemical moiety is one selected from the group consisting of a polymer having a free aldehyde group or a functional group capable of being converted to an aldehyde group, a polymer having a free carboxyl group or a functional group capable of being converted to a carboxyl group, a polymer having a free amine group or a functional group capable of being converted to an amine group, a polymer having a free succinimide group or a functional group capable of being converted to a succinimide group, and a mixture thereof. 
     
     
         26 . The method of  claim 25 , comprising reacting the delivery agent with two flavonoids, wherein the first flavonoid does not undergo association with the second flavonoid. 
     
     
         27 . The method of  claim 25 , wherein the flavonoid is a catechin-based flavonoid. 
     
     
         28 . The method of  claim 27 , wherein the flavonoid is (−)-epicatechin, (−)-epigallocatechin, (+)-catechin, (−)-epicatechin gallate, or (−)-epigallocatechin gallate. 
     
     
         29 . The method of  claim 28 , wherein the flavonoid is (−)-epigallocatechin gallate. 
     
     
         30 . The method of  claim 29 , wherein the (−)-epigallocatechin gallate contains a carboxyl-terminated group, an amine-terminated group, or a succinimide group. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 25 , wherein the polymer is an aldehyde-terminated poly(ethylene glycol), aldehyde-derivatized hyaluronic acid, hyaluronic acid aminoacetylaldehyde diethylacetal conjugate, aldehyde-derivatized hyaluronic acid-tyramine, hyaluronic acid aminoacetylaldehyde diethylacetal conjugate-tyramine, cyclotriphosphazene core phenoxymethyl(methylhydrazono) dendrimer, thiophosphoryl core phenoxymethyl(methylhydrazono) dendrimer, carboxyl-terminated poly(ethylene glycol), amine-terminated poly(ethylene glycol), or succinimide-terminated poly(ethylene glycol). 
     
     
         33 . The method of  claim 32 , wherein the polymer is aldehyde-terminated poly(ethylene glycol). 
     
     
         34 . The method of  claim 33 , comprising reacting the delivery agent with the flavonoid in the presence of an acid catalyst. 
     
     
         35 . The method of  claim 25 , wherein the delivery agent is conjugated at the C6 and/or C8 position of the A ring of the flavonoid. 
     
     
         36 . The method of  claim 25 , wherein the flavonoid is (−)-epigallocatechin gallate and the chemical moiety is poly(ethylene glycol). 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 25 , further comprising a step of loading the delivery agent with an anticancer agent. 
     
     
         39 . The method of  claim 38 , wherein the anti-cancer agent is loaded in the delivery agent through hydrophobic interactions and/or Π-Π stacking interactions with the flavonoid. 
     
     
         40 . The method of  claim 39 , further comprising contacting the delivery agent with a cell. 
     
     
         41 . The method of  claim 40 , wherein the cell is in-vitro. 
     
     
         42 . The method of  claim 40 , wherein the cell is in-vivo and the method comprises administering the delivery agent to a subject in need of anti-cancer treatment. 
     
     
         43 . The method of  claim 42 , wherein the subject is a human. 
     
     
         44 . The method of  claim 42 , wherein the administering comprises injecting, surgically implanting or topically applying. 
     
     
         45 . (canceled) 
     
     
         46 . (canceled)