Liposomal apparatus and manufacturing methods

Abstract

The present invention provides apparatus and processes for producing liposomes. By providing a buffer solution in a first reservoir, and a lipid solution in a second reservoir, continuously diluting the lipid solution with the buffer solution in a mixing chamber produces a liposome. The lipid solution preferably comprises an organic solvent, such as a lower alkanol.

1 . A process for producing a liposome encapsulating a therapeutic product, said process comprising:
 providing an aqueous solution in a first reservoir;   providing an organic lipid solution in a second reservoir, wherein one of the aqueous solution and the organic lipid solution includes a therapeutic product; and   mixing said aqueous solution with said organic lipid solution, wherein said organic lipid solution mixes with said aqueous solution so as to substantially instantaneously produce a liposome encapsulating the therapeutic product.   
     
     
         2 . The process of  claim 1 , wherein said liposome is in a solution having a concentration of about 20% v/v to about 50% v/v organic solvent. 
     
     
         3 . The process of  claim 2 , further comprising further diluting the liposome solution. 
     
     
         4 . The process of  claim 3 , wherein said further dilution is with a buffer. 
     
     
         5 . The process of  claim 3 , wherein said further diluting the liposome solution is a continuous stepwise dilution. 
     
     
         6 . The process of  claim 3 , wherein the liposome solution has a concentration of less than about 25% v/v organic solvent after dilution. 
     
     
         7 . The process of  claim 2 , further comprising removing said organic solvent associated with said liposome solution to form a final form. 
     
     
         8 . The process of  claim 1 , wherein said organic lipid solution comprises an organic solvent. 
     
     
         9 . The process of  claim 8 , wherein said organic solvent is a lower alcohol. 
     
     
         10 . The process of  claim 8 , wherein said organic solvent comprises water. 
     
     
         11 - 46 . (canceled) 
     
     
         47 . An apparatus for producing a liposome encapsulating a therapeutic product, said apparatus comprising:
 a first reservoir for holding an aqueous solution;   a second reservoir for holding an organic lipid solution, wherein one of the aqueous solution and the organic lipid solution includes a therapeutic product; and   a pump mechanism configured to pump said aqueous and said organic lipid solutions into a mixing region at substantially equal flow rates;   wherein the organic lipid solution mixes with said aqueous solution in the mixing region to substantially instantaneously form a therapeutic product encapsulated liposome.   
     
     
         48 . The apparatus of  claim 47 , further including a T-connector defining the mixing region, wherein the aqueous solution and the organic lipid solution are introduced into the T-connector as opposing flows at substantially 180° relative to each other. 
     
     
         49 . The apparatus of  claim 47 , further including a receiving vessel for receiving the therapeutic product encapsulated liposome. 
     
     
         50 . The apparatus of  claim 49 , wherein the liposome is in a solution having a first concentration, the apparatus further including a filtration system coupled to the receiving vessel, said filtration system configured to increase the concentration of the therapeutic product encapsulated liposome solution to a second concentration. 
     
     
         51 . The apparatus of  claim 47 , wherein the therapeutic product is selected from the group consisting of a protein, a plasmid, a nucleic acid, an antisense nucleic acid, a ribozyme, tRNA, snRNA, siRNA, pre-condensed DNA and an antigen. 
     
     
         52 . The apparatus of  claim 47 , wherein the pump mechanism includes a peristaltic pump. 
     
     
         53 . The apparatus of  claim 47 , wherein during mixing, the organic lipid solution undergoes a continuous stepwise dilution in the presence of the aqueous solution. 
     
     
         54 . The apparatus of  claim 47 , wherein the organic lipid solution includes the therapeutic product, and wherein the therapeutic product is lipophilic. 
     
     
         55 . The apparatus of  claim 47 , wherein the aqueous solution includes the therapeutic product. 
     
     
         56 . The apparatus of  claim 47 , wherein the therapeutic product is one of an anionic species and a cationic species.