Drug loaded polymeric nanoparticles and methods of making and using same
View Patent ↗The present disclosure generally relates to methods of making nanoparticles having about 0.2 to about 35 weight percent of a therapeutic agent; and about 10 to about 99 weight percent of biocompatible polymer such as a diblock poly(lactic)acid-poly(ethylene)glycol.
1. A process for preparing therapeutic nanoparticles comprising by:
emulsification of a first organic phase comprising a first polymer and a therapeutic agent, and an aqueous second phase thereby forming an emulsion phase;
quenching the emulsion phase at a temperature of about 0° C. to about 5° C. thereby forming a quenched phase; and
sterile filtration of the quenched phase to recover the therapeutic nanoparticles, wherein the nanoparticles have a diameter of about 80 nm to about 150 nm.
2. The process of claim 1 , wherein the filtration occurs at a temperature of about −5° C. to 10° C.
3. The process of claim 1 , wherein the filtration uses tangential flow filtration.
4. The process of claim 3 , wherein the filtration comprises processing 1 to 6 diavolumes at about 0° C. to about 5° C. and processing at least one diavolume at about 20° C. to 30° C.
5. The process of claim 1 , wherein the first polymer comprises a polylactic acid-polyethylene glycol diblock co-polymer.
6. The process of claim 5 , wherein the polylactic acid portion of the co-polymer has a molecular weight of about 16 kDa, and the polyethylene portion of the co-polymer has a molecular weight of about 5 kDa.
7. The process of claim 1 , wherein the first polymer comprises poly(lactide-co-glycolide)-poly(ethylene glycol) diblock copolymer.
8. The process of claim 1 , wherein the first organic phase further comprises a second polymer.
9. The process of claim 8 , wherein the second polymer is polylactic acid-polyethylene glycol diblock co-polymer or poly(lactide-co-glycolide)-poly(ethylene glycol) diblock copolymer.
10. The process of claim 1 , wherein the emulsification uses a high pressure homogenizer, a rotor stator homogenizer, probe sonicator, or stir bar.
11. The process of claim 10 , wherein homogenizer comprises multiple interaction chambers.
12. The process of claim 1 , wherein the first organic phase has about 5 to 50% solids.
13. The process of claim 1 , wherein the emulsification comprises emulsifying the first organic phase and second aqueous phase to form a coarse emulsion and emulsifying the coarse emulsion to form the emulsion phase.
14. The process of claim 1 , wherein the organic phase comprises a reagent selected from the group consisting of sodium cholate, ethyl acetate, benzyl alcohol or combinations thereof.
15. The process of claim 1 , wherein the therapeutic nanoparticles comprise about 2 to about 30 wt percent therapeutic agent.
16. The process of claim 1 , wherein the therapeutic agent is docetaxel.