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 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 .