Drug loaded polymeric nanoparticles and methods of making and using same
View Patent ↗The present disclosure generally relates to 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. Other aspects of the invention include methods of making such nanoparticles.
1. A therapeutic nanoparticle comprising:
about 0.2 to about 35 weight percent of a therapeutic agent;
about 10 to about 99 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer, wherein said 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, or a diblock poly(lactic)-co-poly (glycolic) acid-poly(ethylene)glycol copolymer, wherein said poly(lactic)-co-poly (glycolic) acid-poly(ethylene)glycol copolymer comprises poly(lactic) -co-poly(glycolic) acid having a number average molecular weight of about 8 to about 12 kDa and poly(ethylene)glycol having a number average molecular weight of about 4 to about 6 kDa; and
about 1 to about 50 weight percent poly(lactic) acid or poly(lactic) acid-co-poly (glycolic) acid, and
wherein the therapeutic nanoparticle releases less than about 10% of the therapeutic agent over 24 hours when placed in a phosphate buffer solution at room temperature.
2. The therapeutic nanoparticle of claim 1 wherein said therapeutic agent is a taxane.
3. The therapeutic nanoparticle of claim 1 , wherein the therapeutic agent is a vinca alkaloid.
4. The therapeutic nanoparticle of claim 3 , wherein the therapeutic agent is vincristine or vinorelbine.
5. The therapeutic nanoparticle of claim 1 , wherein said therapeutic agent is a mTOR inhibitor.
6. The therapeutic nanoparticle of claim 5 , wherein the therapeutic agent is sirolimus, temsirolimus, or everolimus.
7. The therapeutic nanoparticle of claim 1 , wherein the hydrodynamic diameter of therapeutic nanoparticle is about 60 to about 120 nm.
8. The therapeutic nanoparticle of claim 1 , wherein the hydrodynamic diameter is about 70 to about 120 nm.
9. The therapeutic nanoparticle of claim 1 , wherein the therapeutic nanoparticles substantially retains the therapeutic agent for at least 5 days at 25° C.
10. The therapeutic nanoparticle of claim 1 , comprising about 10 to about 20 weight percent of a taxane agent.
11. The therapeutic nanoparticle of claim 1 , comprising about 10 to about 20 weight percent of a vinca alkaloid.
12. The therapeutic nanoparticle of claim 1 , comprising about 10 to about 20 weight percent of sirolimus.
13. The therapeutic nanoparticle of claim 1 , comprising about 40 to about 90 weight percent poly(lactic) acid-poly(ethylene)glycol copolymer.
14. The therapeutic nanoparticle of claim 1 , wherein the particle substantially immediately releases less than about 5% of the therapeutic agent over 1 hour when placed in a phosphate buffer solution at room temperature.
15. A pharmaceutical composition comprising:
a plurality of polymeric nanoparticles each comprising about 0.2 to about 35 weight percent of a therapeutic agent, about 70 to about 99 weight percent of a biocompatible polymer, and optionally a fatty alcohol; wherein the biocompatible polymer is selected from the group consisting of: a combination of poly(lactic) acid-poly(ethylene)glycol copolymer; and poly (lactic) acid or polylactic -co-glycolic acid copolymer;
wherein said 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
a pharmaceutically acceptable excipient, wherein the particle substantially immediately releases less than about 10% of the therapeutic agent over 24 hours when placed in a phosphate buffer solution at room temperature.
16. The pharmaceutical composition of claim 15 , wherein the pharmaceutically acceptable excipient is sucrose.
17. The pharmaceutical composition of claim 15 , wherein said nanoparticles substantially retains the therapeutic agent for at least 5 days at 25° C.
18. The pharmaceutical composition of claim 15 , wherein the therapeutic agent is selected from docetaxel, vincristine, vinorelbine, sirolimus, and temsirolimus.
19. A method of treating prostate or breast cancer comprising administering to a patient in need thereof an effective amount of any of the therapeutic nanoparticles or compositions of claim 1 .
20. A method of treating prostate or breast cancer, comprising administering to a patient in need thereof an effective amount of therapeutic nanoparticles comprising:
about 0.2 to about 35 weight percent of docetaxel;
about 30 to about 90 weight percent poly(lactic) acid-poly(ethylene)glycol copolymer, wherein said 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, or poly(lactic)-co-poly (glycolic) acid-poly (ethylene)glycol copolymer, wherein said poly(lactic)-co-poly (glycolic) acid-poly (ethylene)glycol copolymer comprises poly(lactic) -co-poly(glycolic) acid having a number average molecular weight of about 8 to about 12 kDa and poly(ethylene)glycol having a number average molecular weight of about 4 to about 6 kDa; and
about 5 to about 75 weight percent poly(lactic) acid or poly(lactic) acid-co-poly (glycolic) acid, wherein the therapeutic nanoparticles release less than about 10% of the therapeutic agent over 24 hours when placed in a phosphate buffer solution at room temperature.