Methods of enhancing drug delivery and effectiveness of therapeutic agents

Abstract

The present invention in one aspect provides methods of enhancing uptake of a therapeutic agent in a target tissue as well as methods of treating a disease (such as cancer) or enhancing effectiveness of treatment with a therapeutic agent in an individual by co-administering a composition comprising nanoparticles comprising albumin and a poorly water soluble drug such as a taxane with the therapeutic agent. The present invention in another aspect provides a method of treatment or a method of selecting patients for treatment of a disease (such as cancer) with the combination of a therapeutic agent and a composition comprising nanoparticles comprising albumin and a poorly water soluble drug such as a taxane based on one or more characteristics of the target tissue that correlates or indicates the capability of getting enhanced therapeutic agent uptake as a result of the co-administration of the taxane nanoparticle composition in the target tissue (referred to as “the drug uptake capability”). Also provided are pharmaceutical compositions, article of manufacture, and kits useful for methods described herein.

1 . A method of treating a cancer that is highly fibrotic and/or has a dense stroma in an individual, comprising administering to the individual a) an effective amount of a composition comprising nanoparticles comprising a taxane and an albumin. 
     
     
         2 . The method of  claim 1 , wherein the cancer is a pancreatic cancer, lung cancer, melanoma, or prostate cancer. 
     
     
         3 . The method of  claim 1 , wherein the cancer is selected from the group consisting of: squamous cell carcinomas, mesothelioma, desmoplastic fibroma, desmoplastic round cell tumor, colorectal carcinoma and tumors of gastrointestinal tract. 
     
     
         4 . The method of  claim 1 , wherein the method further comprises administering another therapeutic agent. 
     
     
         5 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the method comprises assessing one or more of the following in the individual prior to administering the taxane nanoparticle composition: a) the amount of tissue stroma, b) tissue vascularization, c) cell/vessel proximity, b) density of tumor matrix, and d) expression of stromal cell markers. 
     
     
         9 . The method of  claim 1 , wherein the target tissue in the individual has any one or more of the following characteristics: 1) high level of albumin uptake; 2) high level of caveolin-1 expression; 3) high level of gp60 expression; and 4) high level of SPARC expression. 
     
     
         10 . The method of  claim 1 , wherein the taxane is paclitaxel. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the nanoparticles in the taxane nanoparticle composition have an average particle size of less than about 200 nm. 
     
     
         13 . The method of  claim 1 , wherein the nanoparticles in the taxane nanoparticle composition comprises a taxane coated with albumin. 
     
     
         14 . (canceled) 
     
     
         15 . A method of treating a disease in an individual, comprising administering to the individual: (a) an effective amount of a composition comprising nanoparticles comprising albumin and a taxane, and (b) an effective amount of a therapeutic agent, wherein drug uptake capability is used as a basis for selecting the individual to receive treatment. 
     
     
         16 . The method of  claim 15 , comprising determining the drug uptake capability of the target tissue in the individual prior to the administration of the taxane nanoparticle composition. 
     
     
         17 . The method of any one of  claims 15 , wherein drug uptake capability is determined based on one or more characteristics selected from the group consisting of: (a) high level of albumin uptake; (b) high level of caveolin-1 expression; (c) high level of gp-60 expression; and (d) high level of SPARC expression. 
     
     
         18 . The method of  claim 15 , wherein the disease is cancer. 
     
     
         19 . The method of  claim 18 , wherein the cancer is a pancreatic cancer, lung cancer, melanoma, or prostate cancer. 
     
     
         20 . The method of  claim 18 , wherein the cancer is selected from the group consisting of: squamous cell carcinomas, mesothelioma, desmoplastic fibroma, desmoplastic round cell tumor, colorectal carcinoma and tumors of gastrointestinal tract. 
     
     
         21 . The method of  claim 15 , wherein the taxane is paclitaxel. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 15 , wherein the nanoparticles in the taxane nanoparticle composition have an average particle size of less than about 200 nm. 
     
     
         24 . The method of  claim 15 , wherein the nanoparticles in the taxane nanoparticle composition comprises a taxane coated with albumin. 
     
     
         25 . The method of  claim 15 , wherein the therapeutic agent is selected from the group consisting of: an antimetabolite, a platinum-based agent, and a prednisone. 
     
     
         26 . A method of assessing responsiveness of an individual to a treatment of a diseases comprising administration of (a) an effective amount of a composition comprising nanoparticles comprising albumin and a taxane and (b) an effective amount of a therapeutic agent, the method comprising determining drug uptake capability of the target tissue in the individual, wherein a drug uptake capability is indicative that the individual is responsive to the treatment. 
     
     
         27 - 28 . (canceled)