Curcumin–Piperine/Curcumin–Quercetin/Curcumin–Silibinin dual drug-loaded nanoparticulate combination therapy: A novel approach to target and treat multidrug-resistant cancers

Abstract

Curcumin is a functional food, which provides a wide range of health benefits including anti-cancer activity and considered as a suitable alternative for chemotherapeutic agents. However, cancer cells exhibit resistance to most chemotherapeutic agents including curcumin due to overexpression of adenosine triphosphate (ATP)-binding cassette transporter proteins in the cancer cell membrane, which decrease the intracellular concentration of chemotherapeutic agents. Similarly, most chemotherapeutic agents including curcumin experience lack of cancer cell targeting, lack of aqueous solubility, rapid systemic clearance, intestinal metabolism and hepatic metabolism. These limitations hinder the clinical usefulness of curcumin in the treatment of multidrug-resistant cancers. In this article, we propose curcumin–piperine, or curcumin–quercetin or curcumin–silibinin dual drug-loaded nanoparticulate combination therapy to target and treat multidrug-resistant cancers. The proposed dual drug-loaded nanoparticulate combination is expected to reverse the multidrug resistance, prevent the rapid systemic clearance, prevent the intestinal and the hepatic metabolism, increase the aqueous solubility, enhance the bioavailability, target the cancer cells, produce a synergistic anti-cancer effect and enhance the efficacy of curcumin in the treatment of multidrug-resistant cancers.