Therapeutic nanoparticles comprising a therapeutic agent and methods of making and using same

Patent metadata

Field	Value
Publication number	US-10080723-B2
Application number	US-201515118737-A
Country	US
Kind code	B2
Filing date	Feb 13, 2015
Priority date	Feb 13, 2014
Publication date	Sep 25, 2018
Grant date	Sep 25, 2018

Abstract

The present disclosure generally relates to nanoparticles comprising a substantially hydrophobic acid, a basic therapeutic agent having a protonatable nitrogen, and a polymer. Other aspects include methods of making and using such nanoparticles.

First claim

What is being claimed is:

1. A therapeutic nanoparticle comprising:
about 0.2 to about 20 weight percent of a basic therapeutic agent having a protonatable nitrogen, wherein the basic therapeutic agent is a tyrosine kinase inhibitor selected from the group consisting of sunitinib, imatinib, nilotinib, dasatinib, bosutinib, ponatinib, bafetinib, and pharmaceutically acceptable salts thereof;
pamoic acid, wherein the molar ratio of the pamoic acid to the basic therapeutic agent is about 0.25:1 to about 2:1; and
about 50 to about 99.75 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer or a diblock poly(lactic acid-co-glycolic acid)-poly(ethylene)glycol copolymer, wherein the therapeutic nanoparticle comprises about 10 to about 30 weight percent poly(ethylene)glycol.

2. The therapeutic nanoparticle of claim 1 , wherein the molar ratio of the pamoic acid to the basic therapeutic agent is about 0.5:1 to about 1.5:1.

3. The therapeutic nanoparticle of claim 1 , wherein the molar ratio of the pamoic acid to the basic therapeutic agent is about 0.75:1 to about 1.25:1.

4. A therapeutic nanoparticle comprising:
a hydrophobic ion-pair comprising pamoic acid and a therapeutic agent having at least one ionizable amine moiety, wherein the therapeutic agent is a tyrosine kinase inhibitor selected from the group consisting of sunitinib, imatinib, nilotinib, dasatinib, bosutinib, ponatinib, bafetinib, and pharmaceutically acceptable salts thereof; and
about 50 to about 99.75 weight percent of a diblock poly(lactic) acid-poly(ethylene)glycol copolymer, wherein the poly(lactic) acid-poly(ethylene)glycol copolymer has a number average molecular weight of about 15 kDa to about 20 kDa poly(lactic acid) and a number average molecular weight of about 4 kDa to about 6 kDa poly(ethylene)glycol.

5. The therapeutic nanoparticle of claim 4 , comprising about 0.05 to about 30 weight percent of the pamoic acid.

6. The therapeutic nanoparticle of claim 4 , wherein the pamoic acid and the therapeutic agent form a hydrophobic ion pair in the therapeutic nanoparticle.

7. The therapeutic nanoparticle of claim 4 , comprising about 2 to about 20 weight percent of the therapeutic agent.

8. The therapeutic nanoparticle of claim 4 , comprising about 10 to about 20 weight percent of the therapeutic agent.

9. The therapeutic nanoparticle of claim 4 , wherein the hydrodynamic diameter of the therapeutic nanoparticle is about 60 to about 150 nm.

10. The therapeutic nanoparticle of claim 4 , wherein the therapeutic agent is selected from the group consisting of dasatinib and pharmaceutically acceptable salts thereof.

11. The therapeutic nanoparticle of claim 9 , wherein the hydrodynamic diameter is about 90 to about 120 nm.

12. The therapeutic nanoparticle of claim 5 , wherein the therapeutic nanoparticle substantially immediately releases less than about 30% of the therapeutic agent when placed in a phosphate buffer solution at 37° C.

13. The therapeutic nanoparticle of claim 5 , wherein the poly(lactic) acid-poly(ethylene)glycol copolymer has a poly(lactic) acid number average molecular weight fraction of about 0.6 to about 0.8.

14. The therapeutic nanoparticle of claim 5 , wherein the therapeutic nanoparticle comprises about 10 to about 25 weight percent poly(ethylene)glycol.

Assignees

• Pfizer

Inventors

• Figueiredo Maria
• Peeke Erick
• Dewitt David
• Van Geen Hoven Christina
• Troiano Greg
• Wright James
• Song Young-Ho
• Wang Hong

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• B82Y40/00

  Manufacture or treatment of nanostructures · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title