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Objective In this study,polybutylcyanoacrylat(PBCA)was synthesized and used as drug carriers.The PBCA nanoparticles loading cisplatin with monomethoxy polyethylene glycol(mPEG M=5000)and different particle size were prepared using double emulsion method.Their physical characteristics were studied.The in vitro anticancer activity of middle size cisplatin-loaded PBCA-mPEG nanoparticles on human hepatocellular cancer hepG2 cells was investigated.The liver targeting of cisplatin-loaded PBCA-mPEG long-circulating nanoparticles was studed in kunmin mouse.Methods Under the basis of single factor experiment,PBCA-mPEG nanoparticles loading cisplatin with mPEG and different particle size were prepared using double emulsion method.The entrapment efficiencies were optimized by uniform design.The nanoparticles were characterized in terms of particle size,zeta potential,entrapment efficiency,drug loading.Cisplatin-loaded PBCA-mPEG nanoparticles of middle particles and higer entrapment efficiency,drug loading had studed.The in vitro anticancer activity of cisplatin-loaded PBCA-mPEG nanoparticles on human hepatocellular cancer hepG2 cells was investigated.60 rats from kunmin were divided into cisplatin-loaded PBCA-mPEG long-circulating nanoparticles groups and free cisplatin groups at random.Cisplatin-PBCA-mPEG freezed-dry dose and cisplatin solution were injected into the veins of rats by the formulation of 5mg/kg. Rats in each group were killed 15,30min,1,2,6and 12 hours respectively after drug was given,cisplatin concentrations were determined using a high effective liquid chromatography with fluorescence detector technique,when obtaining the samples from heart,liver,spleen,lung, kidney,and plasma respectively.Result The nanoparticles were spherical,and particle sizes were about 80nm,170nm and 240nm,respectively.As particle size decreased, zeta potential reduced.Blank PBCA-mPEG nanoparticles exhibited low cytotoxicity,PBCA-mPEG nanoparticles loaded with cisplatin exerted in vitro anticancer activity against hepG2 cells that was comparable to the activity of free(non-entrapped in nanoparticles)cisplatin.Cisplatin released from controlled formulation induced an accumulation of cells in the phase G2/M.These results led to enhance the caspase-3 activity for cisplatin-loaded PBCA-mPEG nanoparticles.The cisplatin concentrations in the lever of rat in the napariticles groups was markedly higher as compared to free cisplatin groups during 12h,whereas the concentration in the kidney was rmarkedly lower than free cisplatin groups(P＜0.01),high concentration in kidney did not,keep long time.Conclusion Cisplatin-loaded PBCA-mPEG long-circulating nanoparticles has low cytotoxicity and the better liver targeting,and the characteristic of low releasing,which decrease the medicine distribution in the kidney and other tissues.So it’s a good medicinediverting system for treating liver cancers.
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