Method for Freeze-Drying Nucleic Acid/Block Copolymer/Cationic Surfactant Complexes

Abstract

This invention relates generally to the freeze-drying of formulations comprising a polynucleotide, a block copolymer and a cationic surfactant. In the presence of a cryoprotectant or bulking agent, a formulation can be freeze-dried, whereby upon reconstitution of the dried formulation, the microparticles maintain their optimal size and aggregation or fusion is avoided.

1 . A method of preparing a lyophilized composition comprising:
 (a) mixing
 (i) a polyoxyethylene (POE) and polyoxypropylene (POP) block copolymer; 
 (ii) a polynucleotide; 
 (iii) a cationic surfactant; and 
 (iv) an amorphous cryoprotectant or a crystalline bulking agent; at a temperature below the cloud point of said block copolymer to form a mixture; and 
   (b) lyophilizing the mixture.   
   
   
       2 . The method of  claim 1 , further comprising a cold filtration step. 
   
   
       3 . The method of  claim 1 , wherein said mixture additionally comprises a pH stabilizing physiologic buffer. 
   
   
       4 . A product produced by the process of  claim 1 . 
   
   
       5 . A stable, mono-dispersed product produced by reconstituting the product of  claim 4  with an aqueous solution. 
   
   
       6 . A product produced by the process of  claim 2 . 
   
   
       7 . A stable, mono-dispersed product produced by reconstituting the product of  claim 6  with an aqueous solution. 
   
   
       8 . A product produced by the process of  claim 3 . 
   
   
       9 . A stable, mono-dispersed product produced by reconstituting the product of  claim 8  with an aqueous solution.