Encapsulation of crocetin into poly (lactic-co-glycolic acid) nanoparticles overcomes drug resistance in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS)

Nanoparticles and herbal medicines have gained considerable attention in overcoming multidrug resistance through different mechanisms. In this study, the effects of poly (Lactic-co-glycolic acid)-crocetin nanoparticles (PLGA-Crt NPs) on MRP1 and MRP2 activity in a human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS) and its parental form (A2780) were evaluated. PLGA-Crt NPs were formulated and then characterized. The cytotoxic effect of Crt, PLGA-Crt NPs, and empty PLGA NPs was assessed using MTT test in A2780 and A2780-RCIS cells. The effect of PLGA-Crt NPs on MRP1 and MRP2 mRNA expression was evaluated by Real-Time qRT-PCR. The impact of PLGA-Crt NPs on the functioning of MRP transporters was assessed by the doxorubicin efflux assay. The particle size, entrapment efficiency (EE) and loading capacity (LC) of PLGA-Crt NPs were obtained about 239.8 +/- 9 nm, 79 +/- 3% and 4.9 +/- 0.2%, respectively. The PLGA-Crt NPs IC50 values were obtained 104 +/- 3 mu M and 96 +/- 2 mu M in A2780 and A2780-RCIS cell lines, respectively. The Real-time RT-PCR results demonstrated the inhibition of mRNA expression of MRP2 in all studied concentrations (up to 67 +/- 8% at 100 mu M) in A2780-RCIS cells. PLGA-Crt NPs showed more indirect efflux inhibition (up to 70 +/- 5%) compared to direct inhibition (up to 49 +/- 5%). The encapsulation of crocetin into PLGA NPs can increase its inhibitory effects on drug resistance by downregulating MRP2 transporters.