Drug loaded polymeric nanoparticles and methods of making and using same

Patent metadata

Field	Value
Publication number	US-9579386-B2
Application number	US-201213659460-A
Country	US
Kind code	B2
Filing date	Oct 24, 2012
Priority date	Jun 16, 2008
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

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.

First claim

The invention claimed is:

1. A therapeutic nanoparticle comprising:
about 4 to about 25 weight percent of a therapeutic agent;
about 10 to about 99 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprising 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 6 kDa;
wherein the hydrodynamic diameter of the therapeutic nanoparticle is about 60 nm to about 140 nm; and
wherein the therapeutic nanoparticles releases less than 2% of the therapeutic agent over about one minute when placed in a phosphate buffer solution at 37° C.

2. The therapeutic nanoparticle of claim 1 , wherein the therapeutic nanoparticle substantially retains the therapeutic agent for at least 3 days at 25° C. when in a solution comprising a saccharide.

3. The therapeutic nanoparticle of claim 2 , wherein the hydrodynamic diameter of therapeutic nanoparticle is about 60 to about 120 nm.

4. The therapeutic nanoparticle of claim 1 , wherein the hydrodynamic diameter is about 70 to about 120 nm.

5. The therapeutic nanoparticle of claim 1 , comprising about 40 to about 90 weight percent poly(lactic) acid-poly(ethylene)glycol copolymer.

6. The therapeutic nanoparticle of claim 1 , wherein the particle releases less than about 10% of the therapeutic agent over 1 hour when placed in a phosphate buffer solution at 37° C.

7. The therapeutic nanoparticle of claim 1 , wherein the particle substantially immediately releases less than about 10% of the therapeutic agent over 30 minutes when placed in a phosphate buffer solution at 37° C.

8. The therapeutic nanoparticle of claim 1 , wherein the therapeutic agent is selected from the group consisting of a taxane, vinorelbine, vinblastine, vincristine and sirolimous.

9. The therapeutic nanoparticle of claim 8 , comprising about 10 to about 20 weight percent of the taxane agent.

10. The therapeutic nanoparticle of claim 9 , wherein the taxane agent is docetaxel.

11. The therapeutic nanoparticle of claim 5 , wherein the poly(lactic) acid of the copolymer has a number average molecular weight of about 16kDa and the poly(ethylene)glycol has a number average molecular weight of about 5kDa.

12. A pharmaceutical composition comprising:
a plurality of polymeric nanoparticles each comprising about 3 to about 40 weight percent of a therapeutic agent, and about 10 to about 99 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprising 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 6 kDa, and having a hydrodynamic diameter of about 60 nm to about 140 nm; and
a saccharide;
wherein said nanoparticles release less than 2% of the therapeutic agent over about one minute when placed in a phosphate buffer solution at 37° C.

13. The pharmaceutical composition of claim 12 , wherein said nanoparticles substantially retains the therapeutic agent for at least 5 days at 25° C.

14. The pharmaceutical composition of claim 12 , comprising sucrose.

15. The pharmaceutical composition of claim 12 , wherein said nanoparticles release less than about 10% therapeutic agent when placed in a phosphate buffer solution at 37° C. for 30 minutes.

16. The pharmaceutical composition of claim 12 , wherein therapeutic nanoparticles comprise about 40 to about 90 weight percent poly(lactic) acid-poly(ethylene)glycol copolymer.

17. The pharmaceutical composition of claim 16 , wherein the therapeutic agent is a chemotherapeutic agent.

18. The pharmaceutical composition of claim 17 , wherein the therapeutic agent is a taxane.

19. The pharmaceutical composition of claim 17 , wherein the therapeutic agent is docetaxel.

20. The therapeutic nanoparticle of claim 17 , wherein the poly(lactic) acid of the copolymer has a number average molecular weight of about 16 kDa and the poly(ethylene)glycol has a number average molecular weight of about 5 kDa.

21. The therapeutic nanoparticle of claim 12 , comprising about 10 to about 30 weight percent of a antineoplastic agent.

22. The therapeutic nanoparticle of claim 12 , comprising about 5 to about 30 weight percent therapeutic agent.

23. A therapeutic nanoparticle comprising:
about 3 to about 40 weight percent of a therapeutic agent;
about 10 to about 99 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer comprising 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 6 kDa;
wherein the hydrodynamic diameter of the therapeutic nanoparticle is about 70 nm to about 130 nm; and
wherein the therapeutic nanoparticles release less than 2% of the therapeutic agent over about one minute when placed in an aqueous solution at 37° C.

24. A method of treating prostate or breast cancer comprising administering to a patient in need thereof an effective amount of the therapeutic nanoparticles of claim 8 .

Assignees

• Pfizer

Inventors

• Zale Stephen E
• Troiano Greg
• Ali Mir Mukkaram
• Hrkach Jeff
• Wright James

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• A61P13/08

  of the prostate · CPC title

• A61K31/475

  having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine (vincamine A61K31/4375) · CPC title