Vehicle for delivering a compound to a mucous membrane and related compositions, methods and systems

Abstract

PSA is delivered to the host by outer membrane vesicles (OMVs), secretion structures that target bacterial molecules to host cells. Purified OMVs direct the in vitro differentiation of functional Tregs with potent suppressive activity in a PSA dependent manner. Treatment of animals with OMVs containing PSA prevents experimental colitis and suppresses pro-inflammatory cytokine responses in the gut, and indicate that compositions, medicaments, and methods useful for the treatment of inflammation, and more particularly, inflammatory bowel diseases.

What is claimed is: 
     
         1 . A pharmaceutical composition for delivering a compound to a mucous membrane comprising an outer membrane vesicle formed by a lipid membrane enclosing an aqueous environment, the vesicle comprising a PSA ligand; and a pharmaceutically appropriate carrier. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the lipid membrane is derived from the plasma membrane of  B. fragilis.    
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the mucous membrane is a mucous membrane of a digestive tract. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the PSA ligand is L-PSA. 
     
     
         5 . The pharmaceutical composition of  claim 1 , further comprising one or more medicaments known to be useful in the treatment inflammatory bowel disease. 
     
     
         6 . The pharmaceutical composition of  claim 1 , further comprising a food composition. 
     
     
         7 . A method of treating an inflammatory disease or inflammation in an individual, comprising administering an effective amount of a composition comprising an outer membrane vesicle formed by a lipid membrane enclosing an aqueous environment, the vesicle comprising a PSA ligand. 
     
     
         8 . The method of  claim 7 , wherein the lipid membrane is derived from the plasma membrane of  B. fragilis.    
     
     
         9 . The method of  claim 7 , further comprising identifying an individual suffering from an inflammatory disease or inflammation. 
     
     
         10 . The method of  claim 7 , wherein the inflammatory disease is inflammatory bowel disease. 
     
     
         11 . The method of  claim 7 , wherein the inflammatory disease is Crohn's disease. 
     
     
         12 . A vesicle for delivering a compound to a mucous membrane, comprising an outer membrane vesicle formed by a lipid membrane enclosing an aqueous environment, the vesicle comprising a PSA ligand. 
     
     
         13 . The vesicle of  claim 12 , further comprising a compound. 
     
     
         14 . The vesicle of  claim 12 , wherein the lipid membrane is derived from the plasma membrane of  B. fragilis.    
     
     
         15 . The vesicle of  claim 12 , wherein the mucous membrane is a mucous membrane of a digestive tract. 
     
     
         16 . The vesicle of  claim 12 , wherein the PSA ligand is L-PSA. 
     
     
         17 . A method for directing the differentiation of functional T regs with potent suppressive activity, comprising an outer membrane vesicle formed by a lipid membrane enclosing an aqueous environment, the vesicle comprising a PSA ligand. 
     
     
         18 . The method of  claim 17 , wherein the PSA ligand is L-PSA. 
     
     
         19 . The method of  claim 17 , wherein said Treg cells inhibit T cell activation. 
     
     
         20 . The method of  claim 17 , wherein the differentiation occurs in vitro. 
     
     
         21 . The method of  claim 17 , further comprising providing dendritic cells. 
     
     
         22 . A method for identifying compounds that reduce inflammation or improve the symptoms of an inflammatory disease in vitro, comprising providing a candidate compound and incubating the compound with Treg cells; further providing T cells, and then determining whether said Treg cells inhibit T cell activation. 
     
     
         23 . The method of  claim 22 , further comprising dendritic cells. 
     
     
         24 . The method of  claim 22 , wherein the Treg cells express Foxp3. 
     
     
         25 . The method of  claim 22 , further determining whether the dendritic cells produce IL-10, and whether such IL-10 production requires the expression of TLR2 on the dendritic cells.