Enhanced delivery of quercetin and doxorubicin using ?-cyclodextrin polymer to overcome P-glycoprotein mediated multidrug resistance

In this study, we prepared a fl-cyclodextrin polymer (fl-CDP) co-loaded quercetin (QCT) and doxorubicin (DOX) nanocarrier (fl-CDP/QD NCs) by freeze-dried method to combat P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in KB-ChR 8-5 cancer cells. Various microscopic and spectroscopic techniques were employed to characterize the prepared nanocarrier. The molecular docking studies confirm the effective binding in-teractions of QCT and DOX with the synthesized fl-CD polymer. The in vitro drug release study illustrates the sustainable release of DOX and QCT from the fl-CDP nanocarrier. Further, we noticed that the QCT released from the fl-CDP nanocarrier improved the intracellular availability of DOX via modulating P-gp drug efflux function in KB-ChR 8-5 cells and MCF-7/DOX cancer cells. Cell uptake results confirmed the successful internalization of DOX in KB-ChR 8-5 cells compared with free DOX. Cell-based assays such as nuclear condensation, alteration in the mitochondrial membrane potential (MMP), and apoptosis morphological changes confirmed the enhanced anticancer effect of fl-CDP/QD NCs in the resistant cancer cells. Hence, QCT and DOX co-loaded fl-CDP may be considered effective in achieving maximum cell death in the P-gp overexpressing MDR cancer cells.