Limit size lipid nanoparticles and related methods

Abstract

Various lipid nanoparticles are disclosed, including nanoparticles comprising a lipid bilayer comprising a phospholipid, a sterol, a polyethylene glycol-lipid surrounding an aqueous core which comprises a therapeutic and/or diagnostic agent and nanoparticles comprising a lipid monolayer surrounding a hydrophobic core. Of particular interest are limit size lipid nanoparticles with a diameter from 10-100 nm. Such lipid nanoparticles are the smallest particles possible for a specific particle composition. Methods and apparatus for preparing such limit size lipid nanoparticles are disclosed.

1 . A limit size lipid nanoparticle wherein the lipid nanoparticle has a diameter from about 10 to about 100 nm. 
     
     
         2 . The nanoparticle of  claim 1 , comprising a lipid bilayer surrounding an aqueous core. 
     
     
         3 . The nanoparticle of  claim 2 , wherein the lipid bilayer comprises a phospholipid. 
     
     
         4 . The nanoparticle of  claim 3 , wherein the phospholipid is a C8-C20 fatty acid diacylphosphatidylcholine. 
     
     
         5 - 6 . (canceled) 
     
     
         7 . The nanoparticle of  claim 3 , comprising from about 50 to about 99 mole percent phospholipid. 
     
     
         8 . The nanoparticle of  claim 2  further comprising a sterol. 
     
     
         9 . The nanoparticle of  claim 8 , wherein the sterol is cholesterol. 
     
     
         10 . The nanoparticle of  claim 9 , comprising from about 10 to about 35 mole percent cholesterol. 
     
     
         11 . The nanoparticle of  claim 2  further comprising a polyethylene glycol-lipid. 
     
     
         12 - 13 . (canceled) 
     
     
         14 . The nanoparticle of  claim 11 , comprising from about 1 to about 10 mole percent polyethylene glycol-lipid. 
     
     
         15 . The nanoparticle of  claim 1 , comprising a lipid monolayer surrounding a hydrophobic core. 
     
     
         16 . The nanoparticle of  claim 15 , wherein the lipid monolayer comprises a phospholipid. 
     
     
         17 . (canceled) 
     
     
         18 . The nanoparticle of  claim 16 , wherein the phospholipid is a C8-C20 fatty acid diacylphosphatidylcholine. 
     
     
         19 . (canceled) 
     
     
         20 . The nanoparticle of  claim 16 , comprising from about 10 to about 70 mole percent phospholipid. 
     
     
         21 . The nanoparticle of  claim 15 , wherein the hydrophobic core comprises a fatty acid triglyceride. 
     
     
         22 . The nanoparticle of  claim 21 , wherein the fatty acid triglyceride is a C8-C20 fatty acid triglyceride. 
     
     
         23 . (canceled) 
     
     
         24 . The nanoparticle of  claim 21  comprising from about 30 to about 90 mole percent fatty acid triglyceride. 
     
     
         25 . The nanoparticle of  claim 2  further comprising a diagnostic agent and/or therapeutic agent. 
     
     
         26 - 36 . (canceled) 
     
     
         37 . A method for administering a therapeutic agent and/or a diagnostic agent to a subject, comprising administering the nanoparticle of  claim 25  to a subject in need thereof. 
     
     
         38 - 91 . (canceled) 
     
     
         92 . The nanoparticle of  claim 11 , wherein the polyethylene glycol-lipid is selected from the group consisting of a PEG-modified phosphatidylethanolamine, a PEG-modified phosphatidic acid, a PEG-modified ceramide, a PEG-modified dialkylamine, a PEG-modified diacylglycerol, and a PEG-modified dialkylglycerol.