Nanocarrier-based co-delivery approaches of chemotherapeutics with natural P-glycoprotein inhibitors in the improvement of multidrug resistance cancer therapy

Abstract

Chemotherapy is the mainstay in cancer treatment; however, its application is clinically limited to patients with multidrug resistance (MDR). MDR reverses the role of chemotherapy through significant attribution to pharmacokinetic characteristics, where ATP-binding cassette transporter proteins, P-glycoprotein (P-gp), pump out the intracellularly transported chemotherapeutics from the cancer cells. Therefore, overexpression of such receptors on MDR cancer cell surfaces tends to decrease the efficacy of a large number of existing chemotherapeutics. P-gp inhibitors, especially of natural origin, play a vital role in enhancing the cellular concentration of clinically applicable chemotherapeutics. Therefore, co-administration of these natural P-gp inhibitors with chemotherapeutics could improve chemotherapeutic efficacy against MDR cancer, which has been evidenced in the literature. Co-delivery of these therapeutic components can effectively be made using the emerging nanotechnology platform, which could facilitate controlled delivery of the incorporated components to the cancerous microenvironment, through passive and active targeting. Thereby, cellular retention of chemotherapeutic agents by the P-gp mediated inhibitory effect on the efflux pump using the nanocarrier co-delivery platform could improve the anticancer potential of the chemotherapeutics. This review has presented the advancement of naturally occurring P-gp inhibitors as a promising adjuvant in chemotherapy to modulate the pharmacokinetic properties of chemotherapeutic agents using the nanotechnology platform.

Keywords: P-glycoprotein inhibitors; Pharmacokinetic modulation; enhanced cancer management; multidrug resistance; reversal of resistance.