Polyphosphazenes, methods of making, and uses thereof

Abstract

Provided are polyphosphazenes and methods of making and using the polyphosphazenes. The polyphosphazenes can be essentially chloride free. The polyphosphazenes can be phosphazene polyacids. The polyphosphazenes can be used as surface coatings, or as adjuvants when combined with antigens.

1 - 33 . (canceled) 
     
     
         34 . A method of enhancing an immunological response to an immunologically active compound in an individual comprising administering one or more compositions comprising a polyphosphazene having the following structure: 
       
         
           
           
               
               
           
         
       
       a salt thereof, or a crosslinked analog thereof,
 wherein R′ and R″ at each occurrence on the polyphosphazene are independently selected from aliphatic; aryl; aralkyl; alkaryl; heteroaromatic; carbohydrates; heteroalkyl; halogen; -oxyaryl; -oxyaliphatic; -oxyfluoroalkyl, -oxyalkaryl, -oxyaralkyl; -thioaryl; thioaliphatic; -thioalkaryl; thioaralkyl; aminoalkyl, aminoaryl, N-ethylpyrrolidone; —NH—[(CH 2 ) x —O-] y -(aryl or aliphatic); and —O—[(CH 2 ) x —O-] y -(aryl or aliphatic); and, 
 wherein n is an integer from 10 to 500,000; x is an in integer from 1 to 8 and v is an integer from 1 to 5,000; and the polyphosphazene has less than 2% by weight chloride. 
 
     
     
         35 . A method of enhancing an immunological response to an immunologically active compound in an individual comprising administering one or more compositions comprising a polyphosphazene having the following structure: 
       
         
           
           
               
               
           
         
       
       a salt thereof, or a crosslinked analog thereof,
 wherein R′ and R″ at each occurrence on the polyphosphazene are independently selected from -phenylCO 2 H, -phenylSO 3 H, -phenylPO 3 H, -(aliphatic)CO 2 H, -(aliphatic)SO 3 H, -(aliphatic)PO 3 H, -phenyl(aliphatic)CO 2 H, -phenyl(aliphatic)SO 3 H, -phenyl(aliphatic)PO 3 H, —[(CH 2 ) x O] y phenylCO 2 H, —[(CH 2 ) x O] y phenylSO 3 H, —[(CH 2 ) x O] y phenylPO 3 H, —[(CH 2 ) x O] y (aliphatic)CO 2 H, —[(CH 2 ) x O] y (aliphatic)SO 3 H, —[(CH 2 ) x O] y (aliphatic)PO 3 H, —[(CH 2 ) x O] y phenyl(aliphatic)CO 2 H, —[(CH 2 ) x O] y phenyl(aliphatic)SO 3 H, -or [(CH 2 ) x O] y phenyl(aliphatic)PO 3 H, 
 wherein n is an integer from 2,500 to 500,000, and the polyphosphazene has a z-average molecular diameter of at least 70 nm in phosphate buffered saline at pH 7.4. 
 
     
     
         36 . The method of  claim 34 , wherein the composition further comprises an immunologically active compound and the immunologically active compound is encapsulated by the polyphosphazene and the polyphosphazene is crosslinked. 
     
     
         37 . The method of  claim 35 , wherein the composition further comprises an immunologically active compound and the immunologically active compound is encapsulated by the polyphosphazene and the polyphosphazene is crosslinked. 
     
     
         38 . The method of  claim 34 , wherein R′ and R″ are at each occurrence on the polyphosphazene are independently selected from -phenylCO 2 H, -phenylSO 3 H, -phenylPO 3 H, -(aliphatic)CO 2 H, -(aliphatic)SO 3 H, -(aliphatic)PO 3 H, -phenyl(aliphatic)CO 2 H, -phenyl(aliphatic)SO 3 H, -phenyl(aliphatic)PO 3 H, —[(CH 2 ) x O] y phenylCO 2 H, —[(CH 2 ) x O] y phenylSO 3 H, —[(CH 2 ) x O] y phenylPO 3 H, —[(CH 2 ) x O] y  (aliphatic)CO 2 H, —[(CH 2 ) x O] y (aliphatic)SO 3 H, —[(CH 2 ) x O] y (aliphatic)PO 3 H, —[(CH 2 ) x O] y phenyl(aliphatic)CO 2 H, —[(CH 2 ) x O] y phenyl(aliphatic)SO 3 H, -or [(CH 2 ) x O] y phenyl(aliphatic)PO 3 H,
 wherein x is an in integer from 1 to 8 and y is an integer from 1 to 5,000. 
 
     
     
         39 . The method of  claim 34 , wherein 0 to 95% of R′ and/or R″ at each occurrence on the polyphosphazene are independently selected from aliphatic; aryl; aralkyl; alkaryl; heteroaromatic; carbohydrates; heteroalkyl; halogen; -oxyaryl; -oxyaliphatic; -oxyalkaryl, -oxyaralkyl; -thioaryl; thioaliphatic; -thioalkaryl; thioaralkyl; aminoalkyl, aminoaryl, N-ethylpyrrolidone; —NH—[(CH 2 ) x —O-] y -(aryl or aliphatic); and —O—[(CH 2 ) x —O-] y -(aryl or aliphatic), and
 wherein 5 to 100% of wherein R′ and R″ are at each occurrence on the polyphosphazene are independently selected from -phenylCO 2 H, -phenylSO 3 H, -phenylPO 3 H, -(aliphatic)CO 2 H, -(aliphatic)SO 3 H, -(aliphatic)PO 3 H, -phenyl(aliphatic)CO 2 H, -phenyl(aliphatic)SO 3 H, -phenyl(aliphatic)PO 3 H, —[(CH 2 ) x O] y phenylCO 2 H, —[(CH 2 ) x O] y phenylSO 3 H, —[(CH 2 ) x O] y phenylPO 3 H, —[(CH 2 ) x O] y  (aliphatic)CO 2 H, —[(CH 2 ) x O] y (aliphatic)SO 3 H, —[(CH 2 ) x O] y (aliphatic)PO 3 H, —[(CH 2 ) x O] y phenyl(aliphatic)CO 2 H, —[(CH 2 ) x O] y phenyl(aliphatic)SO 3 H, -or [(CH 2 ) x O] y phenyl(aliphatic)PO 3 H, 
 wherein x is an in integer from 1 to 8 and y is an integer from 1 to 20 
 
     
     
         40 . The method of  claim 34 , wherein R′ and R″ are carboxylatophenoxy groups or a combination of carboxylatophenoxy groups and trifluoroethoxy groups. 
     
     
         41 . The method of  claim 34 , wherein the polyphosphazene is a salt and the cation is selected from ammonium, potassium, sodium, calcium, iron, magnesium, quaternary ammonium, spermine, spermidine, and combinations thereof. 
     
     
         42 . The method of  claim 34 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         43 . The method of  claim 35 , wherein the polyphosphazene has less than 2% by weight chloride. 
     
     
         44 . The method of  claim 35 , wherein R′ and R″ are carboxylatophenoxy groups or a combination of carboxylatophenoxy groups and trifluoroethoxy groups. 
     
     
         45 . The method of  claim 35 , wherein the polyphosphazene is a salt and the cation is selected from ammonium, potassium, sodium, calcium, iron, magnesium, quaternary ammonium, spermine, spermidine, and combinations thereof. 
     
     
         46 . The method of  claim 35 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         47 . The method of  claim 35 , wherein the composition further comprises one or more salts, wherein the one or more salts do not comprise a chloride ion. 
     
     
         48 . The method of  claim 36 , wherein the immunologically active compound is a vaccine antigen. 
     
     
         49 . The method of  claim 37 , wherein the immunologically active compound is a vaccine antigen.