LIMIT SIZE LIPID NANOPARTICLES AND RELATED METHODS
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.