The aim of the research was to evaluate the influence of two P-glycoprotein (P-gp) inhibitors silymarin and quercetin on anticancer drug doxorubicin (DOX) and pegylated liposomal doxorubicin (PLD) delivery into breast cancer cells (2D cultures) and cancer cell spheroids (3D cultures) at different pH. The cytotoxicity of the compounds was assessed using MTT assay. Spheroids were generated using magnetic 3D Bioprinting method. The uptake of DOX and PLD into monolayer-cultured cells and spheroids was assessed by fluorescence microscopy. Both tested flavonoids did not increase DOX and PLD levels into monolayer-cultured 4T1 cells and 4T1 cell spheroids. However, both silymarin and quercetin enhanced DOX and PLD uptake into JC cell cultures. Silymarin and quercetin may modulate DOX and PLD transport into monolayer-cultured cells and three-dimensional cancer cell cultures depending on P-gp activity.
Keywords: Drug delivery; P-glycoprotein; cell spheroids; multidrug resistance; quercetin; silymarin.
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