Cationic submicron emulsions overcome multidrug resistance in SGC7901/VCR cells.

The over-expression of P-glycoprotein (P-gp) is associated with the development of multi-drug resistance (MDR) in cancer cells. In this study, we examined whether cationic submicron emulsions (CSEs) can efficiently deliver hydroxycamptothecin (HCPT) into MDR cells (SGC7901/VCR cells) via electrostatic-mediated endocytosis, thus overcoming MDR. We prepared HCPT-CSEs and rhodamine-123-CSEs (RH-123-CSEs), and examined the in vitro cytotoxic activity of HCPT-CSEs and the intracellular accumulation of HCPT and RH-123 in SGC7901/VCR cells. The HCPT-CSEs significantly increased the intracellular accumulation of HCPT (8.2-fold higher than HCPT-injection) and enhanced cytotoxic activity of HCPT (2.7-fold higher than HCPT-injection with verapamil). The fluorescence microscopic and flow cytometric detection on RH-123 supported the intracellular accumulation effect of CSEs. These results indicate CSEs may enhance drug-CSEs internalization followed by releasing their contents into the cytoplasm (near nuclear), thus lowering P-gp-mediated drug efflux. Furthermore, these in vitro results suggest that CSEs are a potentially useful drug delivery system to circumvent P-gp-mediated MDR of tumor cells.