Use of umirolimus and its derivatives for treating cancer

Abstract

Novel encapsulated umirolimus and umirolimus polymer conjugate formulations having enhanced permeability and retention at tumor sites. Also provided are methods for treating cancer by administering the umirolimus formulations.

What is claimed is: 
     
         1 . A pharmaceutical formulation comprising umirolimus encapsulated in a liposome, and a pharmaceutically acceptable excipient, carrier, or diluent, wherein the liposome has a particle size of 10-200 nm and includes a polyethylene glycol (PEG) conjugated phospholipid (PEGylated phospholipid) and a phosphatidylcholine (PC), the umirolimus is present at a molar ratio of 0.1-10% based on the amount of the PEGylated phospholipid and the PC, and the PEG has a length of 10-3000 monomeric units. 
     
     
         2 . The formulation of  claim 1 , wherein the PEG has a length of 40-150 monomeric units. 
     
     
         3 . The formulation of  claim 1 , wherein the PEGylated phospholipid is selected from the group consisting of PEG-distearoylphosphatidylcholine (PEG-DSPC), PEG-distearoylphosphatidylethanolamine (PEG-DSPE), PEG-distearoylphosphatidylglycerol (PEG-DSPG), PEG-dimyristoylphosphatidylcholine (PEG-DMPC), PEG-dioleoylphosphatidylcholine (PEG-DOPC), PEG-dioleoylphosphatidylethanolamine (PEG-DOPE), and PEG-dipalmitoylphosphatidylglycerol (PEG-DPPG). 
     
     
         4 . The formulation of  claim 3 , wherein the PC is hydrogenated soy PC (HSPC), egg PC, or soy PC. 
     
     
         5 . The formulation of  claim 4 , wherein the PEGylated phospholipid is PEG-DSPE, the PC is HSPC, and a molar ratio between the umirolimus, the PEGylated phospholipid, and the PC is 10:60:30. 
     
     
         6 . The formulation of  claim 4 , further comprising cholesterol, wherein the phospholipid is PEGylated phospholipid is PEG-DSPE, the PC is HSPC, the umirolimus is present at the molar ratio of 0.1-2%, and a molar ratio between the PEGylated phospholipid, the PC, and the cholesterol is 55-65:2-10:20-40. 
     
     
         7 . The formulation of  claim 2 , wherein the PEGylated phospholipid is selected from the group consisting of PEG-DSPC, PEG-DSPE, PEG-DSPG, PEG-DMPC, PEG-DOPC, PEG-DOPE, and PEG-DPPG. 
     
     
         8 . The formulation of  claim 7 , wherein the PC is HSPC, egg PC, or soy PC. 
     
     
         9 . The formulation of  claim 8 , wherein the PEGylated phospholipid is PEG-DSPE, the PC is HSPC, and a molar ratio between the umirolimus, the PEGylated phospholipid, and the PC is 10:60:30. 
     
     
         10 . The formulation of  claim 8 , further comprising cholesterol, wherein the phospholipid is PEGylated phospholipid is PEG-DSPE, the PC is HSPC, the umirolimus is present at the molar ratio of 0.1-2%, and a molar ratio between the PEGylated phospholipid, the PC, and the cholesterol is 55-65:2-10:20-40. 
     
     
         11 . A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer. 
     
     
         13 . A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of  claim 2 . 
     
     
         14 . The method of  claim 13 , wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer. 
     
     
         15 . A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of  claim 5 . 
     
     
         16 . The method of  claim 15 , wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer. 
     
     
         17 . A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of  claim 6 . 
     
     
         18 . The method of  claim 17 , wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer. 
     
     
         19 . A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of  claim 9 . 
     
     
         20 . The method of  claim 19 , wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer. 
     
     
         21 . A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of  claim 10 . 
     
     
         22 . The method of  claim 21 , wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer.