Processes and systems for preparing cellular or viral membranes and nanoparticles
The present invention relates to processes and systems for preparing nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles using or comprising, inter alia, a multi-inlet vortexing reactor, tangential flow filtration (TFF) and/or a high shear fluid processor such as a microfluidizer (or a microfluidizer processor). The present invention also relates to the nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles prepared by the present processes and systems, and the uses and/or applications of the nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles.
1 . A process for preparing a nanoparticle, which process comprises:
1) mixing a polymer for forming a nanoparticle in an organic solvent and an aqueous phase comprising water or a water-based buffer using a multi-inlet vortexing reactor to form a composition comprising said nanoparticle wherein said organic solvent dissolves said polymer and is miscible with water; and
2) subjecting said composition to tangential flow filtration (TFF) to remove said organic solvent from said composition.
2 . The process of claim 1 , wherein the polymer is poly(lactic-co-glycolic acid) (PLGA).
3 . The process of claim 1 , wherein the polymer is selected from the group consisting of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylysine, polyglutamic acid and a hydrophobic polymer that coils when switched from an organic solvent to an aqueous phase.
4 . The process of claim 1 , wherein the polymer has a level ranging from about 0.01 mg/mL to about 40 mg/mL in the multi-inlet vortexing reactor in step 1).
5 . The process of claim 1 , wherein the organic solvent is acetonitrile or acetone.
6 . The process of claim 1 , wherein the organic solvent has a level ranging from about 1% (v/v) to about 50% (v/v) in the multi-inlet vortexing reactor in step 1).
7 . The process of claim 1 , wherein the multi-inlet vortexing reactor comprises a reaction chamber and multiple tangentially arranged inlets, through which the material for forming a nanoparticle in an organic solvent and/or an aqueous phase are injected into the reaction chamber.
8 . The process of claim 1 , wherein the organic solvent phase has a flow rate ranging from about 1 mL/minute to about 1,000 mL/minute in the multi-inlet vortexing reactor in step 1).
9 . The process of claim 1 , wherein the aqueous phase has a flow rate ranging from about 1 mL/minute to about 1,000 mL/minute in the multi-inlet vortexing reactor in step 1).
10 . The process of claim 1 , wherein step 1) and/or 2) are conducted at a temperature ranging from about 0° C. to about 40° C.
11 . The process of claim 1 , wherein the nanoparticle has a hydrodynamic size or diameter from about 10 nm to about 10 μm.
12 . The process of claim 1 , wherein the nanoparticle has a polydispersity index (PDI) from about 0.1 to about 0.7.
13 . The process of claim 1 , wherein the TFF is conducted using a TFF system that comprises a feed reservoir, a filter device and a collection device, the feed reservoir is in fluid communication with the filter device via an inlet on the filter device, the filter device is in fluid communication with the collection device via a permeate outlet on the filter device, and the filter device is in fluid communication with the feed reservoir via a retentate outlet on the filter device.
14 . The process of claim 1 , wherein the TFF is conducted via a diafiltration process.
15 . The process of claim 1 , wherein the TFF is conducted using a feeding rate ranging from about 0.1 mL/minute to about 1,000 mL/minute.
16 . The process of claim 1 , wherein the TFF is conducted using a feeding pressure ranging from about 0.1 psi to about 100 psi.
17 . The process of claim 1 , wherein the TFF is conducted using a retentate pressure ranging from about 0.1 psi to about 100 psi.
18 . The process of claim 1 , wherein the TFF is conducted within a time ranging from about 10 minutes to about 10 hours.
19 . The process of claim 1 , wherein:
the TFF is used to remove from about 50% to about 99.9999% of the organic solvent from the composition, or
the TFF is used to concentrate and/or enrich the nanoparticle from about 1 fold to about 100 fold.
20 . The process of claim 1 , which is used to prepare the nanoparticle at a production rate ranging from about 0.1 g/hour to about 1,000 g/hour for one production batch.