Protozoan variant-specific surface proteins (vsp) as carriers for oral drug delivery

Abstract

The invention provides compositions for oral delivery and methods of treatment using VSP carriers, such as Giardia sp. variable surface proteins (VSP), to deliver therapeutic agents. VSP drug carriers can be combined with bioactive peptides, e.g., glucagon, or hGH, and be administered orally or mucosally. VSP carriers are resistant to acidic pHs and to proteolytic degradation and protect therapeutic agents from degradation in the gastrointestinal tract.

1 - 60 . (canceled) 
     
     
         61 . A therapeutic composition comprising a VSP (Variant-specific Surface Protein) carrier or VSP-like carrier and a bioactive peptide, wherein
 (i) the VSP carrier or VSP-like carrier can bind to the bioactive peptide;   (ii) the VSP carrier or VSP-like carrier is not covalently bound to the bioactive peptide via a peptidic bond;   (iii) the bioactive peptide is therapeutically effective after binding to the VSP carrier or VSP-like carrier;   (iv) the binding of the VSP carrier or VSP-like carrier to the bioactive peptide increases the resistance of the bioactive peptide to pH-mediated and/or enzymatic degradation compared to the resistance of the same bioactive peptide not bound to said VSP carrier or VSP-like carrier; and,   (v) the bioactive peptide is not a vaccine immunogen.   
     
     
         62 . The therapeutic composition of  claim 61 , wherein the bioactive peptide is a cytokine or a peptide hormone. 
     
     
         63 . The therapeutic composition of  claim 62 , wherein the cytokine is an interleukin. 
     
     
         64 . The therapeutic composition of  claim 63 , wherein the interleukin is interleukin-2 (IL-2) or interleukin-10 (IL-10). 
     
     
         65 . The therapeutic composition of  claim 63 , wherein the cytokine is an interferon. 
     
     
         66 . The therapeutic composition of  claim 61 , wherein the VSP carrier is a VSP from  Giardia.    
     
     
         67 . The therapeutic composition of  claim 61 , wherein the VSP-like carrier is a VSPs-like protein from  Tetrahymena, Entamoeba , or  Paramecium.    
     
     
         68 . The therapeutic composition of  claim 61 , formulated for oral or mucosal administration. 
     
     
         69 . The therapeutic composition of  claim 61 , wherein the VSP carrier comprises the extracellular domain of a VSP from  Giardia  or a fragment thereof. 
     
     
         70 . The therapeutic composition of  claim 61 , wherein the VSP-like carrier comprises the extracellular domain of a VSP-like protein from  Tetrahymena  or a fragment thereof. 
     
     
         71 . The therapeutic composition of  claim 61 , wherein the VSP-like carrier comprises the extracellular domain of a VSP-like protein from  Paramecium  or a fragment thereof. 
     
     
         72 . The therapeutic composition of  claim 61 , wherein the VSP-like carrier comprises the extracellular domain of a VSP-like protein from  Entamoeba  or a fragment thereof. 
     
     
         73 . The therapeutic composition of  claim 61 , wherein the VSP carrier or VSP-like carrier further comprises a protein purification tag sequence. 
     
     
         74 . The therapeutic composition of  claim 62 , wherein peptide hormone is insulin, human growth hormone, glucagon, or parathormone. 
     
     
         75 . The therapeutic composition of  claim 61 , wherein the molecule to molecule ratio of VSP carrier or VSP-like carrier to the bioactive peptide ranges from about 10:1 to about 1:10. 
     
     
         76 . A pharmaceutical composition comprising the therapeutic composition of  claim 61  and a pharmaceutically acceptable excipient. 
     
     
         77 . A method of delivering a bioactive peptide to a target location in a subject in need thereof comprising orally administering the therapeutic composition of  claim 61  to the subject. 
     
     
         78 . A method of treating a disease or condition in a subject in need thereof comprising orally administering an effective amount of the therapeutic composition of  claim 61  to the subject. 
     
     
         79 . A method of treating a disease or condition in a subject in thereof comprising combining a VSP carrier or VSP-like carrier and a bioactive peptide, wherein
 (i) the VSP carrier or VSP-like carrier can bind to the bioactive peptide;   (ii) the VSP carrier or VSP-like carrier is not covalently bound to the bioactive peptide via peptidic bonds;   (iii) the bioactive peptide is therapeutically effective after binding to the VSP carrier, wherein the binding of the VSP carrier or VSP-like carrier to the bioactive peptide increases the resistance of the bioactive peptide to pH-mediated and/or enzymatic degradation compared to the resistance of the same bioactive peptide not bound to said VSP carrier or VSP-like carrier; and,   (iv) the bioactive peptide is a cytokine or a peptide hormone.   
     
     
         80 . A method of making an orally deliverable composition comprising combining a VSP carrier or VSP-like carrier and a bioactive peptide, wherein
 (i) the VSP carrier or VSP-like carrier can bind to the bioactive peptide;   (ii) the VSP carrier or VSP-like carrier is not covalently bound to the bioactive peptide via peptidic bonds;   (iii) the bioactive peptide is therapeutically effective after binding to the VSP carrier, wherein the binding of the VSP carrier or VSP-like carrier to the bioactive peptide increases the resistance of the bioactive peptide to pH-mediated and/or enzymatic degradation compared to the resistance of the same bioactive peptide not bound to said VSP carrier or VSP-like carrier; and,   (iv) the bioactive peptide is a cytokine or a peptide hormone.