Compositions and methods for bile acid particles

Abstract

Therapeutic compositions are disclosed which contain a therapeutic agent and a bile acid or bile acid conjugate. The compositions can be absorbed via enterohepatic circulation. The compositions include a cationic moiety and an anionic polymer, which are coupled through electrostatic interactions. The therapeutic compositions can be used for the treatment of diseases or disorders.

1 . A therapeutic composition comprising:
 a core complex comprising a therapeutic agent and having an exterior surface with a net positive charge at a pH of 5; and   a bile acid or a bile acid conjugate covalently bound to an anionic polymer;   wherein the anionic polymer has a net negative charge at neutral pH, and   wherein the anionic polymer is electrostatically coupled to the exterior surface.   
     
     
         2 . The composition of  claim 1 , wherein the therapeutic agent comprises a nucleic acid. 
     
     
         3 . The composition of  claim 2 , wherein the nucleic acid comprises a gene. 
     
     
         4 . The composition of  claim 3 , wherein the gene encodes GLP-1 or Exendin 4. 
     
     
         5 . The composition of  claim 1 , wherein the therapeutic agent comprises a peptide. 
     
     
         6 . The composition of  claim 5 , wherein the peptide is insulin. 
     
     
         7 . The composition of  claim 1 , wherein the therapeutic agent is a small molecule. 
     
     
         8 . The composition of  claim 6 , wherein the small molecule is doxorubicin. 
     
     
         9 . The composition of  claim 1 , wherein the therapeutic agent comprises a vaccine or virus. 
     
     
         10 . The composition of  claim 1 , wherein the core complex comprises a cationic polymer. 
     
     
         11 . The composition of  claim 10 , wherein the cationic polymer is selected from at least one of polyethylenimine, protamine, or poly(lysine). 
     
     
         12 . The composition of  claim 1 , wherein the core complex comprises a cationic liposome. 
     
     
         13 . The composition of  claim 12 , wherein the cationic liposome comprises a cationic lipid. 
     
     
         14 . The composition of  claim 1 , wherein the anionic polymer comprises hyaluronic acid, chondroitin sulfate, or heparin. 
     
     
         15 . The composition of  claim 1 , wherein the bile acid or bile acid conjugate comprises a cholic acid. 
     
     
         16 . The composition of  claim 15 , wherein the cholic acid is taurocholic acid. 
     
     
         17 . A method of delivering a therapeutic agent to a cell, the method comprising oral administration of the therapeutic composition of  claim 1  to a subject. 
     
     
         18 . The method of  claim 17 , wherein the therapeutic composition is absorbed by the subject through a bile acid transporter in the gastrointestinal tract of the subject, and
 wherein the therapeutic composition enters the enterohepatic circulatory system of the subject.   
     
     
         19 . A method of treating cancer, the method comprising orally administering the therapeutic composition of  claim 1  to a subject, wherein the therapeutic agent is an anticancer agent. 
     
     
         20 . A method of treating a metabolic disorder, the method comprising administering the therapeutic composition of  claim 1  to a subject, wherein the therapeutic agent is selected from at least one of GLP-1, Exendin 4, or insulin.