Preparation and evaluation of paclitaxel and Brucea javanica oilcore-matched nanoemulsions to treat cancer in vitro and in vivo

摘要

Objective： Developed the core-matched nanoemulsions （CMNEs） to co-delivery paclitaxel-oleic acid （PTX-OA） prodrug and Brucea javanica oil （BJO） for increasing the antitumor effect.Methods： Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy whichbased on core-matched technology （CMT） were evaluated in vitro and in vivo.Results： The PTX-OA/BJO CMNEs were of nanoscale particle size （108.7±2.3） nm and with entrapmentefficiency of 〉95%. The PTX-OA/B]O CMNEs displayed concentration and time-dependent cytotoxicityagainst HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of thetumor volume with no obvious toxicity was observed in nude mice model following administration ofPTX-OA/BJO CMNEs compared with the control treated with normal saline （P〈0.05）, which suggestedthe excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEswere associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibitingtumor cell proliferation and the activity of TOPO II.Conclusion： Co-encapsulation of two drugs with different mechanisms allows simultaneous interruptionof diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity.