SELECTIVE TARGETING AND SENSITIZATION OF MDR CELLS USING ULTRASONIC-ACTIVATED MICELLAR DRUG DELIVERY

摘要

Encapsulation in Pluronic P-105 micelles substantially enhanced the intracellular uptake of doxorubicin (DOX ) by MDR A2780/ADR cells while suppressing DOX uptake by drug-sensitive A2780 cells. Application of low-frequency ultrasound enhanced the uptake of the micellar-encapsulated drug for both MDR and sensitive cells. The intracellular DOX distribution in MDR cells differed from that of a structurally related anthracyclin drug, ruboxyl (Rb). When delivered from RPMI 1640 or PBS, DOX penetrated into nuclei of MDR cells but Rb did not. Encapsulation in Pluronic micelles affected the intracellular trafficking of Rb resulting in its accumulation in the nuclei of MDR cells. For all systems, the intracellular drug uptake was enhanced by ultrasound. Micellar delivery combined with ultrasound resulted in a substantial decrease of IC_(50) for Rb and DOX in MDR cells.