KMID : 0369820110410060381
|
|
Jorunal of Korean Pharmaceutical Sciences 2011 Volume.41 No. 6 p.381 ~ p.386
|
|
Combination of Curcumin and Paclitaxel-loaded Solid Lipid Nanoparticles to Overcome Multidrug Resistance
|
|
Li Rihua
Xu Wenting Lee Mi-Kyung
|
|
Abstract
|
|
|
Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.
|
|
KEYWORD
|
|
MDR, p-glycoprotein, Curcumin, Paclitaxel
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|