WO/2008/036117 | NANOGEL CONTRAST AGENTS FOR OPTICAL MOLECULAR IMAGING |
JP6368301 | Ultrafine nanoparticles as a multi-modal contrast agent |
WO/2003/103594 | MICELLE ASSEMBLIES |
AMENDED CLAIMS received by the International Bureau on 22 September 2014 (22.09.14) 1. A method for preparing lipid nanoparticles (LNP), the method comprising: a) introducing i) one or more streams of a lipid solution via a first set of one or more inlet ports of a manifold and ii) one or more streams of an aqueous solution via a second set of two or more inlet ports of the manifold, thereby mixing the lipid solution and the aqueous solution so as to produce an LNP solution; and b) recovering the LNP solution via one or more outlet ports of the manifold; wherein the angle between at least one lipid and at one aqueous solution inlet ports is not 180° or a substantially similar angle and at least two aqueous solution inlet ports and at least one lipid solution inlet port are not in the same plane. 2. The method of claim 1 , wherein the angle between at least one lipid and at one aqueous solution inlet ports is about 120° or less. 3. The method of clam 1, wherein the aqueous solution in step ii) is introduced via at least two inlet ports. 4. The method of claim 3, wherein the aqueous solution in step ii) is introduced via at least 3 but no more than 11 inlet ports. 5. The method of clam 3, wherein at least two aqueous inlet ports and at least one lipid solution inlet port are in the same plane. 6. The method of claim 5, wherein at least one outlet port is substantially perpendicular to the plane of inlet ports. 7. The method of clam 5, wherein at least one outlet port is substantially not perpendicular to the plane of inlet ports. 8. The method of claim 3, wherein at least two aqueous solution inlet ports and at least two lipid solution inlet ports are not in the same plane. 9. The method of claim 1 , wherein the lipid solution and/or the aqueous solution is introduced at a flow rate of about 1 ml/min to 6,000 ml/min. 10. The method of claim 9, wherein the lipid solution and/or the aqueous solution is introduced via port size of 0.1-5 mm at a flow rate about 1 ml/min to about 2,500 ml/min. 11. The method of claim 1 , wherein the flow velocity of the lipid solution and/or the aqueous solution is the lipid solution and/or the aqueous solution is from about 0.002 m/s to about 10 m s. 12. The method of claim 1, wherein the LNP solution comprises substantially lipid discs. 13. The method of claim 1, wherein the LNP solution comprises substantially liposomes. 14. The method of claim 1, wherein the mean particle size of LNP is from about 10 nm to about 2,000 nm. 15. The method of claim 1 , wherein the LNP have a polydispersity index from about 0.0005 to about 0.5. 16. The method of claim 1, wherein the lipid solution comprises lipids dissolved in an organic solvent. 17. The method of claim 1, wherein the organic solvent is ethanol at a concentration of about 70% or more. 18. The method of claim 16, wherein the concentration of total lipids in the lipid solution is in the range from about 1 mg/ml to about 200 mg/ml. 19. The method of claim 1 , wherein one of the lipids in the lipid solution is chosen from anionic lipid, cationic lipid, or neutral lipid. 20. The method of claim 3, wherein the aqueous solution introduced into at least one of the inlet ports differs from a second aqueous solution introduced into another inlet port. 21. The method of claim 1 , wherein the aqueous solution and/or the lipid solution comprises an active pharmaceutical ingredient (API). 22. The method of claim 1 , wherein step a) further comprises introducing iii) one or more streams of non-aqueous solutions via one or more inlet ports of the manifold. 23. The method of claim 1, further comprising step c) loading LNP recovered from the LNP solution with an API. 24. The method of claim 21 or claim 23, wherein the API is a small molecule, a peptide, a protein, RNA, or DNA. 25. The method of claim 21 or claim 23, wherein the API is an anticancer agent, an antibiotic agent, an antiviral agent, an anti-fungal agent, or an analgesic. 26. The method of claim 25, wherein the anti-cancer agent is chosen from daunorubicin, doxorubicin, paclitaxel, docetaxel, cisplatin, carboplatin, cytarabine, floxuridine, fludarabine, fmorouracil, iproplatin, leuprolide acetate, and methotrexate. 27. The LNP solution made by the method of claim 1. 28. A pharmaceutical composition prepared using the LNP solution of claim 26. 33 A device adapted to perform the method of claim 1. 34 |