Therapeutic polymeric nanoparticles comprising vinca alkaloids and methods of making and using same
View Patent ↗The present disclosure generally relates to therapeutic nanoparticles. Exemplary nanoparticles disclosed herein may include about 1 to about 20 weight percent of a vinca alkaloid; and about 50 to about 99 weight percent biocompatible polymer.
1. A therapeutic nanoparticle comprising:
about 9 to about 16 weight percent of vinorelbine or a pharmaceutically acceptable salt thereof; and
about 70 to about 90 weight percent biocompatible polymer, wherein the biocompatible polymer is
a diblock poly(lactic) acid-poly(ethylene)glycol copolymer, wherein said diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprises poly(lactic acid) having a number average molecular weight of about 15 to 20 kDa and poly(ethylene)glycol having a number average molecular weight of about 4 to about 6 kDa and
wherein the diameter of the therapeutic nanoparticle is about 70 to about 140 nm.
2. The therapeutic nanoparticle of claim 1 , wherein the diameter is about 80 to about 130 nm.
3. The therapeutic nanoparticle of claim 1 , wherein the particle releases less than about 7% of the vinorelbine, over about 1 minute to about 30 minutes, when placed in a phosphate buffer solution at room temperature.
4. The therapeutic nanoparticle of claim 1 , wherein the particle releases less than about 10% of the vinorelbine, over about 1 minute to about 30 minutes, when placed in a phosphate buffer solution at 37° C.
5. The therapeutic nanoparticle of claim 1 , wherein said diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprises poly(lactic acid) having a number average molecular weight of about 16 kDa and poly(ethylene)glycol having a number average molecular weight of about 5 kDa.
6. A therapeutic nanoparticle comprising:
about 2 to about 20 weight percent of vincristine or vinorelbine, or a pharmaceutically acceptable salt thereof;
a diblock polymer of poly(lactic) acid-poly(ethylene)glycol copolymer; wherein said diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprises poly(lactic acid) having a number average molecular weight of about 15 to 20 kDa and poly(ethylene)glycol having a number average molecular weight of about 4 to about 6 kDa,
wherein the diameter of the nanoparticle is about 70 to about 140 nm.
7. The therapeutic nanoparticle of claim 6 , comprising about 9 to about 16 weight percent of vinorelbine or a pharmaceutically acceptable salt thereof.
8. The therapeutic nanoparticle of claim 6 , comprising about 3 to about 9 weight percent of vinorelbine or a pharmaceutically acceptable salt thereof.
9. The therapeutic nanoparticle of claim 6 , wherein the particle releases less than about 4% of the vincristine or vinorelbine, or a pharmaceutically acceptable salt thereof, over about 1 minute to about 30 minutes when placed in a phosphate buffer solution at room temperature.
10. The therapeutic nanoparticle of claim 6 , wherein the particle releases less than about 2% of the vincristine or vinorelbine, or a pharmaceutically acceptable salt thereof, over about 1 minute to about 30 minutes when placed in a phosphate buffer solution at room temperature.
11. The therapeutic nanoparticle of claim 6 , further comprising cetyl alcohol.
12. A pharmaceutically acceptable composition comprising a plurality of therapeutic nanoparticles of claim 6 ; and
a pharmaceutically acceptable excipient.
13. The pharmaceutically acceptable composition of claim 12 , wherein the pharmaceutically acceptable excipient is a sugar.
14. The pharmaceutically acceptable composition of claim 13 , wherein the pharmaceutically acceptable excipient is sucrose.
15. A method of treating prostate, breast, or non-small cell lung cancer, comprising administering to a patient in need thereof an effective amount of a composition comprising the therapeutic nanoparticle of claim 1 .