Effect simultaneous delivery with P-glycoprotein inhibitor and nanoparticle administration of doxorubicin on cellular uptake and in vitro anticancer activity

Ozgur Esim; Meral Sarper; Cansel K Ozkan; Sema Oren; Baris Baykal; Ayhan Savaser; Yalcin Ozkan

doi:10.1016/j.jsps.2020.02.008

Effect simultaneous delivery with P-glycoprotein inhibitor and nanoparticle administration of doxorubicin on cellular uptake and in vitro anticancer activity

Saudi Pharm J. 2020 Apr;28(4):465-472. doi: 10.1016/j.jsps.2020.02.008. Epub 2020 Feb 17.

Authors

Ozgur Esim¹, Meral Sarper², Cansel K Ozkan¹, Sema Oren², Baris Baykal³, Ayhan Savaser¹, Yalcin Ozkan¹

Affiliations

¹ University of Health Sciences, Gulhane Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey.
² University of Health Sciences, Gulhane Institute of Health Sciences, Ankara, Turkey.
³ University of Health Sciences, Gulhane Faculty of Medicine, Department of Histology and Embryology, Ankara, Turkey.

Abstract

Multidrug resistance (MDR) is the most common problem of inadequate therapeutic response in tumor cells. Many trials has been developed to overcome drug efflux by P-glycoprotein (P-gp). For instance, co-administration of a number of drugs called chemosensitizers or MDR modulators with a chemotherapeutic agent to inhibit drug efflux. But for optimal synergy, the drug and inhibitor combination may need to be temporally colocalized in the tumor cells. In this study, we encapsulated the Ver and Dox in PLGA nanoparticles to inhibit the P-gp drug efflux in breast cancer. Moreover, the effect of either Dox solution (Dox_S), Dox nanoparticles (Dox_NP), Dox_S + Ver_S, Dox_NP + Ver_S, Dox_NP + Ver_NP or Dox-Ver_NP was evaluated. It was found that co administration of Dox_NP with Ver_NP (70.76%) showed similar cellular uptake of Dox to Dox/Ver combination solution (70.62%). However it is observed that Dox_NP + Ver_NP has the highest apoptotic activity (early apoptotic 13.52 ± 0.06%, late apoptotic 53.94 ± 0.15%) on human breast adenocarcinoma (MCF 7) cells. Hence, it is suggested that Dox_NP + Ver_NP is a promising administration for tumor therapy.

Keywords: Doxorubicin; Nanoparticle; P-glycoprotein; Verapamil.