Methods of treating central nervous system disorders via administration of nanoparticles of an mTOR inhibitor and an albumin
The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent).
1. A method of treating a central nervous system (CNS) disorder in an individual, comprising systemically administering to the individual an effective amount of a composition comprising nanoparticles comprising a mammalian target of rapamycin (mTOR) inhibitor and an albumin, wherein the CNS disorder is epilepsy.
2. The method of claim 1 , wherein the nanoparticle composition is administered once every week, twice every three weeks, or three times every four weeks.
3. The method of claim 1 , wherein the average diameter of the nanoparticles in the nanoparticle composition is no greater than about 200 nm.
4. The method of claim 1 , wherein the weight ratio of the albumin to the mTOR inhibitor in the nanoparticle composition is no greater than about 9:1.
5. The method of claim 1 , wherein the nanoparticles comprise the mTOR inhibitor coated with the albumin.
6. The method of claim 1 , wherein the nanoparticle composition is administered for at least about one to six cycles, wherein each cycle consists of 21 days or 28 days.
7. The method of claim 1 , wherein the mTOR inhibitor is a limus drug.
8. The method of claim 7 , wherein the mTOR inhibitor is rapamycin.
9. The method of claim 7 , wherein the epilepsy is a medically refractory or surgically refractory epilepsy.
10. The method of claim 7 , wherein the nanoparticle composition is administered to the individual at a dose of about 0.1 mg/m 2 to 25 mg/m 2 .
11. The method of claim 7 , wherein the nanoparticle composition is administered to the individual at a dose of about 1 mg/m 2 to 10 mg/m 2 and wherein the nanoparticle composition is administered once every week, twice every three weeks, or three times every four weeks.
12. The method of claim 1 , further comprising administering to the individual an effective amount of a second agent selected from the group consisting of an anti-VEGF antibody, an alkylating agent and a proteasome inhibitor.
13. The method of claim 12 , wherein the second agent is an anti-VEGF antibody.
14. The method of claim 12 , wherein the second agent is a proteasome inhibitor.
15. The method of claim 12 , wherein the second agent is an alkylating agent.
16. The method of claim 1 , wherein the individual is a human.
17. The method of claim 1 , wherein the nanoparticle composition is parenterally administered into the individual.
18. The method of claim 17 , wherein the nanoparticle composition is intravenously administered into the individual.
19. The method of claim 17 , wherein the nanoparticle composition is subcutaneously administered into the individual.