Methods and formulations for the delivery of pharmacologically active agents

Abstract

In accordance with the present invention, novel formulations have been developed which are much more effective for the delivery of hydrophobic drugs to patients in need thereof than are prior art formulations. Invention formulations are capable of delivering more drug in shorter periods of time, with reduced side effects caused by the pharmaceutical carrier employed for delivery.

That which is claimed is: 
     
         1 . A formulation comprising nanoparticles comprising paclitaxel and albumin which is free of cremophor, wherein the size of the nanoparticles is in the range of 20-400 nm, and wherein said formulation is characterized by one or more of the following:
 wherein said formulation provides a higher concentration of paclitaxel in the cellular compartment than a formulation of paclitaxel with cremophor;   wherein said formulation provides increased intra-cellular availability of paclitaxel relative to a formulation of paclitaxel with cremophor;   wherein said formulation provides a higher concentration maximum (Cmax) for paclitaxel in tumor cells than does a formulation of paclitaxel with cremophor;   wherein said formulation enhances delivery of paclitaxel to a tumor tissue relative to a formulation of paclitaxel with cremophor; and   wherein said formulation enhances delivery of paclitaxel to pancreas, prostate, kidney, lung, heart, bone, or spleen relative to a formulation of paclitaxel with cremophor.   
     
     
         2 . The formulation of  claim 1 , wherein the albumin is human serum albumin. 
     
     
         3 . The formulation of  claim 1 , wherein said formulation enhances delivery of paclitaxel to a tumor tissue relative to a formulation of paclitaxel with cremophor. 
     
     
         4 . The formulation of  claim 3 , wherein said formulation enhances delivery of paclitaxel to pancreas, kidney, lung, heart, bone, or spleen relative to a formulation of paclitaxel with cremophor. 
     
     
         5 . A formulation comprising nanoparticles comprising paclitaxel and albumin which is free of cremophor, wherein the size of the nanoparticles is in the range of 20-400 nm, wherein upon administration of said formulation the area under curve of paclitaxel increases proportionally with the dose of paclitaxel between about 55 mg/m2 and about 158 mg/m2. 
     
     
         6 . The formulation of  claim 5 , wherein the albumin is human serum albumin. 
     
     
         7 . The formulation of  claim 5 , wherein upon administration of said formulation the area under curve of paclitaxel increases proportionally with the dose of paclitaxel between about 55 mg/m2 and about 700 mg/m2. 
     
     
         8 . The formulation of  claim 5 , wherein said administration is intravenous administration. 
     
     
         9 . A method of administration comprising administering formulation comprising nanoparticles comprising paclitaxel and albumin which is free of cremophor, wherein the size of the nanoparticles is in the range of 20-400 nm, and wherein said formulation is characterized by one or more of the following:
 wherein said formulation provides a higher concentration of paclitaxel in the cellular compartment than a formulation of paclitaxel with cremophor;   wherein said formulation provides increased intra-cellular availability of paclitaxel relative to a formulation of paclitaxel with cremophor;   wherein said formulation provides a higher concentration maximum (Cmax) for paclitaxel in tumor cells than does a formulation of paclitaxel with cremophor;   wherein said formulation enhances delivery of paclitaxel to a tumor tissue relative to a formulation of paclitaxel with cremophor; and   wherein said formulation enhances delivery of paclitaxel to pancreas, prostate, kidney, lung, heart, bone, or spleen relative to a formulation of paclitaxel with cremophor.   
     
     
         10 . The method of  claim 9 , wherein the albumin is human serum albumin. 
     
     
         11 . The method of  claim 9 , wherein said formulation enhances delivery of paclitaxel to a tumor tissue relative to a formulation of paclitaxel with cremophor. 
     
     
         12 . The method of  claim 11 , wherein said formulation enhances delivery of paclitaxel to pancreas, kidney, lung, heart, bone, or spleen relative to a formulation of paclitaxel with cremophor. 
     
     
         13 . The method of  claim 9 , wherein said administration is intravenous administration. 
     
     
         14 . A method of administration comprising administering a formulation comprising nanoparticles comprising paclitaxel and albumin which is free of cremophor, wherein the size of the nanoparticles is in the range of 20-400 nm, and upon administration of said formulation the area under curve of paclitaxel increases proportionally with the dose of paclitaxel between about 55 mg/m2 and about 158 mg/m2. 
     
     
         15 . The method of  claim 14 , wherein the albumin is human serum albumin. 
     
     
         16 . The method of  claim 14 , wherein upon administration of said formulation the area under curve of paclitaxel increases proportionally with the dose of paclitaxel between about 55 mg/m2 and about 700 mg/m2. 
     
     
         17 . The method of  claim 14 , wherein said administration is intravenous administration.