The Preparation Of Berbamine-paclitaxel Nanoparticles And Evaluation Of Its Synergistic Antitumor Effect In Vitro

Objectives: To evaluate the effect of Berbamine (BA) and Paclitaxel (PTX) on human gastric cancer cell lines. The nanoparticles loading BA or BA together with PTX were prepared from methoxy poly(ethylene-glycol)-polycaprolactone (mPEG-PCL) by nanopreticipation method. The physiochemical properties, release properties and the in vitro synergistic antitumor effect of the nanoparticles was evaluated to elucidate the superiorty of polymeric nanoparticles in the treatment of cancer and the prospect of this nanoscale controlled release drug delivery system.Methods: Median effect analysis was employed to determine the interaction between BA and PTX by analyzing the relationship between fraction affected (Fa) and the combination index (CI) acquired from the dose-effect curve. The amphiphilic block copolymer was prepared by ring opening polymerization. The o/w emulsion method was applied to prepare BA-loaded nanoparticles. The structure and molecular weight of the copolymer as well as the shape, diameter and in vitro release properties of the nanoparticles was studied. The synergistic antitumor effect of the nanoparticles on gastric cancer cell lines MKN-28 and BGC-823 was determined using MTT assay.Results: Both BA and PTX inhibited the growth of MKN-28 and BGC-823 cells. Synergistic effect of BA and PTX was observed, which was more obvious at lower concentrations. The BA-PTX nanoparticles was spherical with the diameter less than 100nm. The maximum loading content and encapsulating efficiency of BA were 15.28% and 87±3.4%, respectively. The nanoparticles exhibited sustained release pattern as to the in vitro release test. The nanoparticles entered cells via endocytosis, which was proved in the cellular uptake studies. BA nanoparticles showed similar cytotoxicity compared to BA free drug with concentration and time dependence. The BA-PTX nanoparticles was also smaller than 100nm. The maximum loading content and encapsulating efficiency of PTX were 16.9±2.1% and 16.9±2.1%, which were 14.8±1.9% and 84.7±7.4% as to BA. The release profile of the double nnaoparticles was also sustainable. As to the cytotoxicity against BGC-823 cell lines, the double nanoparticles showed much more prominent effectiveness compared to free PTX. This confirmed that BA and PTX showed satisfactory effect after being loaded into the copolymeric nanoparticles. Conclusions: BA can reinforce the antitumor effect of PTX on gastric cancer cell lines. At the same time, the BA-loaded and BA-PTX-loaded nanoparticles showed sustained release pattern as well as synergistic antitumor effect in vitro, which implied the prospect of this drug delivery system.