Therapeutic polymeric nanoparticle compositions with high glass transition temperature or high molecular weight copolymers
View Patent ↗The present disclosure relates in part to pharmaceutical compositions comprising polymeric nanoparticles having certain glass transition temperatures. Other aspects of the invention include methods of making such nanoparticles.
1. A method of treating a solid tumor cancer in a patient in need thereof, comprising administering to said patient a pharmaceutical aqueous suspension comprising a therapeutically effective amount of therapeutic nanoparticles, wherein said therapeutic nanoparticles comprise:
about 4 to about 25% by weight of an anti-cancer agent;
about 40 to about 99% by weight of poly(D,L-lactic)acid-poly(ethylene)glycol copolymer;
and
about 0.2 to about 10 mole percent PLA-PEG-ligand; wherein the pharmaceutical aqueous suspension has a glass transition temperature between about 39 and 41° C.
2. The method of claim 1 , wherein between about 50% and about 70% of the anti-cancer agent is released from the therapeutic nanoparticles as determined at a four hour time point in an in vitro dissolution test at 37° C.
3. The method of claim 1 , wherein the poly(ethylene)glycol portion of the copolymer has a number average molecular weight of about 4 kDa to about 6 kDa.
4. The method of claim 1 , wherein the poly(D,L-lactic) acid portion of the copolymer has a number average molecular weight of about 16 kDa, and the poly(ethylene)glycol portion of the copolymer has a number average molecular weight of about 5 kDa.
5. The method of claim 4 , wherein the anti-cancer agent is docetaxel.
6. The method of claim 1 , wherein the anti-cancer agent is selected from the group consisting of vinca alkaloids, nitrogen mustard agents, mTOR inhibitors, and boronate esters or peptide boronic acid compounds.
7. The method of claim 1 , comprising about 50 to about 90% by weight of the poly( D,L -lactic)acid-poly(ethylene)glycol copolymer.
8. A method of treating a solid tumor cancer in a patient in need thereof, comprising administering by injection to said patient a pharmaceutical aqueous suspension comprising a therapeutically effective amount of therapeutic nanoparticles, wherein said therapeutic nanoparticles comprise:
about 4 to about 25% by weight of an anti-cancer agent;
about 50 to about 90% by weight of poly( D,L -lactic)acid-poly(ethylene)glycol copolymer; and
about 0.2 to about 10 weight percent poly(lactic)acid-poly(ethylene)glycol covalently bound to a targeting ligand; wherein the therapeutic nanoparticles have a glass transition temperature between about 39 and 41° C.
9. The method of claim 8 , wherein the targeting ligand is represented by:
10. The method of claim 8 , where the patient is suffering from breast, ovarian, lung, or prostate cancer.
11. The method of claim 8 , wherein the therapeutic nanoparticles have a diameter of about 80 nm to about 130 nm.