Prion free nanoparticle compositions and methods of making thereof

Abstract

The present invention provides prion-free compositions comprising nanoparticles comprising albumin and substantially water insoluble drugs. Also provided are methods of making prion-free compositions and methods of removing prion proteins from the nanoparticle compositions. Methods of using the compositions, as well as kits useful for carrying out the methods are also provided.

1 . A composition comprising nanoparticles comprising albumin and a substantially water insoluble pharmacologically active agent, wherein the composition is substantially free of a prion protein. 
     
     
         2 . The composition of  claim 1 , wherein the composition has a prion infectivity of less than about 100 fg/ml. 
     
     
         3 . The composition of  claim 1 , wherein the composition has a prion infectivity of less than about 10 IU-ic/ml. 
     
     
         4 . The composition of  claim 1 , wherein the composition does not show the presence of a prion protein based on a protein misfolding cyclic amplification (PMCA) assay or based on an IPCR assay. 
     
     
         5 . The composition of  claim 1 , further comprising a trace amount of a ligand capable of binding to a prion protein. 
     
     
         6 . A composition comprising nanoparticles comprising albumin and a substantially water insoluble pharmacologically active agent, wherein the albumin in the composition was obtained by a method comprising a prion removal process, said prion removal process comprising contacting an initial albumin composition with a ligand capable of binding to a prion protein. 
     
     
         7 . The composition of  claim 6 , wherein the prion removal process further comprises removing said ligand and proteins bound thereto from said albumin and composition. 
     
     
         8 . The composition of  claim 7 , wherein the ligand is a peptide. 
     
     
         9 . The composition of  claim 7 , wherein the ligand is a trazine-based compound. 
     
     
         10 . A method of producing a composition comprising nanoparticles comprising albumin and a substantially water insoluble pharmacologically active agent, said method comprising: a) removing a prion protein from an initial albumin composition; b) subjecting a mixture comprising a solution comprising the prion-removed albumin and an organic phase comprising said substantially water insoluble pharmacologically active agent dispersed in an organic solvent to a high shear condition. 
     
     
         11 . The method of  claim 10 , wherein step a) comprises: 1) contacting the initial albumin solution with a ligand capable of binding to a prion protein. 
     
     
         12 . The method of  claim 11 , wherein step a) further comprises: 2) removing the ligand and proteins bound thereto from the albumin solution. 
     
     
         13 . The method of  claim 11 , further comprising removing said organic solvent from the mixture. 
     
     
         14 . The method of  claim 11 , wherein said ligand is a peptide. 
     
     
         15 . The method of  claim 11 , wherein the ligand is a triazine-based compound. 
     
     
         16 . The method of  claim 10 , wherein the initial albumin composition is a blood derived product. 
     
     
         17 . A method of producing a composition comprising nanoparticles comprising albumin and a substantially water insoluble pharmacologically active agent, comprising: a) subjecting a mixture comprising an organic phase comprising said substantially water insoluble pharmacologically active agent and an albumin solution to a high shear condition, and b) removing a prion protein from said mixture. 
     
     
         18 . The method of  claim 17 , wherein step b) comprises: 1) contacting the mixture with a ligand capable of binding to a prion protein. 
     
     
         19 . The method of  claim 18 , wherein step b) further comprises: 2) removing the ligand and proteins bound thereto from said mixture. 
     
     
         20 . The method of  claim 18 , wherein said ligand is a peptide. 
     
     
         21 . The method of  claim 18 , wherein the ligand is a triazine-based compound. 
     
     
         22 . A method of removing a prion protein from a composition suspected of containing a prion protein comprising nanoparticles comprising albumin and a substantially water insoluble pharmacologically active agent, comprising: a) contacting the composition with a ligand capable of binding to a prion protein, b) removing the ligand and proteins bound thereto from the composition.