| Objective Primary liver cancer is one of the most common malignant tumors of human.Because of its onset, a high degree of malignancy, infiltration and metastasis.Most of thepatients haves been found in the late level and lose the opportunities of operationtreatment, There is an urgent need to find an effective treatment method.In recent yearsultrasound-trigger drug delivery for tumor therapy is a research hot spot. This projectaims to explore the feasibility and effectiveness of the treatment of liver cancer bypreparing the docetaxel-loaded lipid microbubbles and investigating the proliferationinhibition and apoptosis induction effect of microbubble combining ultrasound on in vitrohuman hepatocellular carcinoma HepG2cells.Methods The drug-loaded microbubbles in this study was manufactured by thin-filmhydration method using the phospholipids as membrane material, C3F8as wrapped gasand docetaxel as drug. The encapsulation efficiency as index,the optimal process of ratewas selected by using single factor test of phospholipids and docetaxel drug ratio, the ratioof phospholipids and cholesterol, the temperature of the rotary evaporation, the temperature and time of hydration and mechanical shock time. The microbubblemorphology and particle size was detected by scanning electron microscope andtransmission electron microscope.entrapment efficiency and drug loading were evaluatedby HPLC and the stability of4℃and25℃was investigated, in vivo contrast effect wasobserved by US. In the in vitro experiments,survival effect of docetaxel on humanhepatocellular carcinoma HepG2cells was detected by CCK-8method. The proliferationinhibition of each group on cell was detected by CCK-8method.The morphology of eachgroup cell apoptosis was observed using the inverted microscope. The cycle and apoptosisof each group cell was detected by flow cytometry. The variation in microstructure of eachgroup cells was observed by transmission electron microscope.Results Docetaxel-loaded lipid microbubbles showed round shape, dispersion, noadhesion, uniform size, particle diameter in a range of200~650nm, encapsulation rate of(85.72±2.68)%and the amount of drug loading of (14.29±1.17)%. The property ofmicrobubles was stable for10days when preserved at4℃, particle diameter in a range of230~700nm, encapsulation rate of (80.25±2.26)%and the amount of drug loading of(13.37±1.13)%.The in vivo experiment of microbubbles showed contrast enhancementeffect and then crease in MI was found to destruct the microbubbles. Results in vitroexperiments showed that docetaxel can significantly affect the survival of humanhepatocellular carcinoma HepG2cells,And the cell survival rate in a dose effectrelationship with drug concentration and action time.The proliferation inhibition andapoptosis induction effect of docetaxel-loaded lipid microbubbles combining ultrasoundon the of human hepatoma HepG2cells was more significant than other experimentalgroups, Smily use the docetaxel-loaded lipid microbubbles was non proliferationinhibition and apoptosis induction effect on human hepatoma HepG2cells, and themicrobubbles would only release drug under the insonation of ultrasonund.Conclusion Docetaxel-loaded lipid microbubbles are safe, highly efficient and stable drugcarriers. The combination of this type of microbubbles with ultrasound induced inhibitionof proliferation and apoptosis effect on the human hepatoma HepG2cells was moresignificant than docetaxe, Effect of docetaxel-loaded lipid microbubbles are expected to become a new and effective drug delivery path of argeting tumor therapy. |
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