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.

Description

RELATED APPLICATIONS[0001]This application claims priority benefit to U.S. Provisional Patent Application No. 61 / 318,777, filed on Mar. 29, 2010, incorporated herein by reference in its entirety.TECHNICAL FIELD[0002]The present invention relates to methods of enhancing drug delivery and effectiveness of therapeutic agent(s) by administering compositions comprising nanoparticles that comprise albumin and a poorly water insoluble drug such as a taxane.BACKGROUND[0003]Taxanes (such as paclitaxel and docetaxel) are a class of diterpenoid drugs that have anti-tumor activity against a wide range of human cancers. Paclitaxel was originally isolated from the bark of the Yew tree, and was known to act by interfering with the normal function of microtubule breakdown. Paclitaxel binds to the β subunit of tubulin, the building blocks of microtubules, causing hyper-stabilization of the microtubule structures. The resulting paclitaxel / microtubule structure is unable to disassemble, thereby arrest...

AI Technical Summary

Benefits of technology

[0008]In some embodiments, there is provided a method of treating a disease (such as cancer) in an individual, comprising administering to the individual an effective amount of a therapeutic agent and a composition comprising nanoparticles comprising albumin and a taxane, wherein the uptake of the therapeutic agent to a target tissue (such as tumor) is enhanced compared to the uptake of the therapeutic agent not co-administered with the taxane nanoparticle composition.

[0009]In some embodiments, there is provided a method of treating an individual having a tumor (such as solid tumor), comprising administering to the individual an effective amount of a therapeutic agent and a composition comprising nanoparticles comprising albumin and a taxane, wherein the uptake of the therapeutic agent to the tumor is enhanced compared to the uptake of the therapeutic agent not co-administered with the taxane nanoparticle composition.

[0010]In some embodiments, there is provided a method of facilitating the uptake of a therapeutic agent to a target tissue (such as tumor) in an individual, comprising administering to the individual the therapeutic agent in conjunction with a composition comprising nanoparticles comprising an albumin and a taxane. In some embodiments, there is provided a method of facilitating the uptake of a therapeutic agent to a tumor (such as solid tumor) in an individual, comprising administering to the individual the therapeutic agent in conjunction with a composition comprising nanoparticles comprising an albumin and a taxane.

[0012]Also provided herein are methods of creating a microenvironment in a target tissue (such as tumor) in an individual that facilitates delivery of other therapeutic agent(s), i.e., therapeutic agent other than the drug in the nanoparticle composition. For example, in some embodiments, there is provided a method of altering the microenvironment of a target tissue (such as tumor) to facilitate uptake of a therapeutic agent, comprising administering to the individual a composition comprising nanoparticles comprising albumin and a taxane. In some embodiments, there is provided a method of reducing (such as disrupting, for example depleting) tumor stroma in an individual having a tumor, comprising administering to the individual a composition comprising nanoparticles comprising albumin and a taxane. In some embodiments, there is provided a method of increasing tumor vascularization in an individual having a tumor, comprising administering to the individual a composition comprising nanoparticles comprising albumin and a taxane. In some embodiments, there is provided a method of increasing cell / vessel proximity in an individual having a tumor, comprising administering to the individual a composition comprising nanoparticles comprising albumin and a taxane. In some embodiments, there is provided a method of loosening (such as disrupting, for example destroying) the tumor matrix in an individual having a tumor, comprising administering to the individual a composition comprising nanoparticles comprising albumin and a taxane.

Problems solved by technology

Paclitaxel binds to the β subunit of tubulin, the building blocks of microtubules, causing hyper-stabilization of the microtubule structures.

Therapeutic agents, especially cancer drugs, often suffer in overall effectiveness due to problems associated with delivery / access to target tumor sites.