Abstract
ObjectiveDeveloped the core-matched nanoemulsions (CMNEs) to co-delivery paclitaxel-oleic acid (PTX-OA) prodrug and Brucea javanica oil (BJO) for increasing the antitumor effect. MethodsAntitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology (CMT) were evaluated in vitro and in vivo. ResultsThe PTX-OA/BJO CMNEs were of nanoscale particle size (108.7 ± 2.3) nm and with entrapment efficiency of >95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline (P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPO Ⅱ. ConclusionCo-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity.
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