Purified therapeutic nanoparticles and preparation methods thereof

Abstract

Purified therapeutic nanoparticles are provided herein. Such nanoparticles comprise an active pharmaceutical ingredient and human serum albumin, wherein the weight ratio of human serum albumin to the active ingredient in the therapeutic nanoparticles is from 0.01:1 to 1:1, and wherein the nanoparticles are substantially free of free human serum albumin that is not incorporated in the nanoparticles. The present disclosure also provides pharmaceutical compositions that comprise the purified therapeutic nanoparticles and are also substantially free of free human serum albumin. Methods for preparing and using the purified therapeutic nanoparticles and compositions thereof are also provided.

1 . Purified therapeutic nanoparticles, comprising an active ingredient and human serum albumin (HSA), wherein the weight ratio of HSA to the active ingredient in the therapeutic nanoparticles is selected from 0.01:1, 0.02:1, 0.025:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.10:1, 0.11:1, 0.12:1, 0.13:1, 0.14:1, 0.15:1, 0.16:1, 0.17:1, 0.18:1, 0.19:1, 0.2:1, 0.21:1, 0.22:1, 0.23:1, 0.24:1, 0.25:1, 0.26:1, 0.27:1, 0.28:1, 0.29:1, 0.3:1, 0.31:1, 0.32:1, 0.33:1, 0.34:1, 0.35:1, 0.36:1, 0.37:1, 0.38:1, 0.39:1, 0.4:1, 0.41:1, 0.42:1, 0.43:1, 0.44:1, 0.45:1, 0.46:1, 0.47:1, 0.48:1, 0.49:1, 0.5:1, 0.51:1, 0.52:1, 0.53:1, 0.54:1, 0.55:1, 0.56:1, 0.57:1, 0.58:1, 0.59:1, 0.6:1, 0.65:1, 0.70:1, 0.75:1, 0.8:1, 0.85:1, 0.9:1, 0.95:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1 or the range between any two ratios above, wherein the active ingredient is encapsulated inside HSA and wherein the therapeutic nanoparticles are substantially free of free HSA that is not incorporated in the nanoparticles, and wherein the average particle size of the therapeutic nanoparticles is from 110 to 150 nm. 
     
     
         2 . The therapeutic nanoparticles according to  claim 1 , wherein the weight ratio of human serum albumin to the active ingredient is selected from 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 0.10:1, 0.11:1, 0.12:1, 0.13:1, 0.14:1, 0.15:1, 0.16:1, 0.17:1, 0.18:1, 0.19:1, 0.2:1, 0.21:1, 0.22:1, 0.23:1, 0.24:1, 0.25:1, 0.26:1, 0.27:1, 0.28:1, 0.29:1, 0.3:1, 0.31:1, 0.32:1, 0.33:1, 0.34:1, 0.35:1, 0.36:1, 0.37:1, 0.38:1, 0.39:1, 0.4:1, 0.41:1, 0.42:1, 0.43:1, 0.44:1, 0.45:1, 0.46:1, 0.47:1, 0.48:1, 0.49:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, or the range between any two ratios above. 
     
     
         3 . The therapeutic nanoparticles according to  claim 1 , wherein the nanoparticles contain at most 5% free HSA (by weight). 
     
     
         4 . The therapeutic nanoparticles according to  claim 1 , wherein the active ingredient has the properties of being insoluble or slightly soluble in water, but soluble or free soluble in an organic solvent. 
     
     
         5 . The therapeutic nanoparticles according to  claim 4 , wherein the active ingredient is selected from taxanes, macrolides, camptothecins, anthracycline antibiotics, colchicine, thiocolchicine dimer, amiodardone, liothyronine, cyclosporine, exemestane, flutamide, fulvestrant, romidepsin, semustine, and ibuprofen. 
     
     
         6 . The therapeutic nanoparticles according to  claim 5 , wherein the active ingredient is a taxane. 
     
     
         7 . The therapeutic nanoparticles according to  claim 5 , wherein the taxane is paclitaxel or docetaxel. 
     
     
         8 . The therapeutic nanoparticles according to  claim 4 , wherein the organic solvent is a pure solvent having low water-solubility and low boiling point or its mixture with small molecular alcohols. 
     
     
         9 . A pharmaceutical composition, comprising the therapeutic nanoparticles according to  claim 1 , wherein the composition is substantially free of free HSA that is not incorporated in the nanoparticles. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the pharmaceutical composition is in the form of liquid or lyophilized powder. 
     
     
         11 . The pharmaceutical composition according to  claim 9 , wherein the pharmaceutical composition also comprises lyophilization excipient when the pharmaceutical composition is in the form of lyophilized powder. 
     
     
         12 . The pharmaceutical composition according to  claim 11 , wherein the lyophilization excipient is selected from one or more of mannitol, sucrose, lactose, maltose, trehalose, and dextran. 
     
     
         13 . The pharmaceutical composition according to  claim 9 , wherein the composition contains at most 5% free HSA (by weight). 
     
     
         14 . The pharmaceutical composition according to  claim 9 , wherein the active ingredient is paclitaxel. 
     
     
         15 . A method for treating cancer, comprising:
 administering a therapeutically effective amount of the therapeutic nanoparticles according to  claim 1  to a subject in need thereof.   
     
     
         16 . The method according to  claim 15 , wherein the cancer is selected from the group consisting of liver cancer, prostatic cancer and lung cancer. 
     
     
         17 . The method according to  claim 15 , wherein the active ingredient is selected from the group consisting of taxanes, macrolides, camptothecins, anthracycline antibiotics, colchicine, thiocolchicine dimer, amiodardone, liothyronine, cyclosporine, exemestane, flutamide, fulvestrant, romidepsin, semustine, and ibuprofen. 
     
     
         18 . The method according to  claim 15 , wherein the active ingredient is taxane. 
     
     
         19 . The method according to  claim 15 , wherein the active ingredient is paclitaxel or docetaxel. 
     
     
         20 . The method according to  claim 15 , wherein the nanoparticles contain at most 5% free HSA (by weight).