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OBJECTIVE:To study the in vitro uptake of Resibufogenin(RBG)lactic acid glycolic acid copolymer-water solu-ble vitamin E (PLGA-TPGS) in human liver cancer HepG2 cells,mouse ascites-type lymphatic metastasis of tumor HCa-F cells, and the toxicity on HepG2 cells. METHODS:RCPTN loading RBG and coumarin-6(C6)were prepared. Fluorescent inverted mi-croscope was used to observe the in vitro uptake by RCPTN HepG2,HCa-F cells. It was divided into negative control group,blank PLGA-TPGS nanoparticles(EPTN)group,5-fluorouracil solution(FS)group,RBG solution(RS)group,RBG/PLGA nanoparti-cles(RPN)group and RPTN group. WST-1 was conducted to investigate the optical density at 450 nm wavelength of HepG2 cells after 24,48,72 h incubated by FS,RS,RPN and RPTN with different final concentrations (1.25,2.5,5,10,20 μg/mL);the cell viability (CV) and half inhibitory concentration (IC50) were calculated. RESULTS:RCPTN distributed around the nucleus of HepG2,HCa-F cells. CV was decreased by RBG concentration increased in RPN group and RPTN group,and decreased by time prolonged;compared with FS group,CV in RPTN group was decreased(PFS>RPN>RPTN;IC50 incubated by RPN and RPTN for 48,72 h was obviously less than that of FS and RS(P<0.05 or P<0.01). CONCLUSIONS:RPTN can deliver RBG in-to HepG2,HCa-F cells,showing inhibition effect on HepG2 cells which is stronger than RPN,RS and FS.
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Objective To investigate the therapeutic effects of Quercetin (QT)-loaded PLGA-TPGS nanoparticles (QPTN) on solid tumor-bearing mice with HCa-F hepatocarcinoma in vivo.Methods The model of HCa-F hepatocarcinoma solid tumor-bearing mice was established by implanting HCa-F cells into 48 mice.The mice were divided into 6 groups randomly:the negative control,empty PLGA-TPGS nanoparticles,5-Fluorouracil solutions (FS),Quercetin solutions (QTS),QT-loaded PLGA nanoparticles (QPN),and QPTN groups.Each group was treated using tail vein twice a day for 20 days;then,all mice were sacrificed.The increment tumor volumes and tumor growth inhibition rate were counted.Then,tumor specimens were prepared for hematoxylin & eosin (HE) staining and observed under a microscope.Results The results showed that the increment tumor volumes of mice in the QPTN,QPN,and FS groups were significantly smaller than that in the negative control group (P ＜ 0.05 or P ＜ 0.01).The tumor growth inhibition rate of the QPTN group was 59.07％,which was much higher than that of the QTS group (23.94％),the FS group (35.14％),and the QPN group (46.14％).The results of the HE staining on the tumor sections also indicated that the QPTN group showed a better therapeutic outcome compared to the other groups.Conclusion The QPTN has a better therapeutic effect on the model of solid tumor using HCa-F cells-bearing mice than the QPN,QTS,and FS.
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Objective The aim of this study was to investigate the distribution and liver-targeting properties of quercetin (QT)/coumarin 6 (C6)-loaded polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (QCPTN) in a hepatocarcinoma ectopic transplantation solid tumor model using HCa-F cell-bearing mice.Methods The QT concentrations in biological samples were determined using reverse phase-high performance liquid chromatography (RP-HPLC) analysis.After intravenous administration to mice in the QCPTN and QTS groups,the QT concentration in plasma and in different tissues was simultaneously analyzed at the different time points.Detection indexes (relative targeting efficiency,Re;targeting efficiency,Te) and fluorescence inversion microscopy images of the frozen tissue (liver,solid tumor,spleen,lungs,kidneys,and heart) slices were used for quantitatively and qualitatively evaluating the liver-targeting properties of QCPTN in solid tumor-bearing mice.Results Te of the QCPTN group in the plasma,liver,solid tumor,spleen,lungs,kidneys,and heart were all greater than 3,indicating that the area under the concentration-time curve (AUC) of liver was more than three times that of the plasma and other organs.Fluorescence inversion microscopy images showed that the green fluorescence of QCPTN was mostly observed in the liver.Conclusion Using HCa-F cell-beating mice,QCPTN was found to have better in vivo liver-targeting properties in hepatocarcinoma ectopic transplantation solid tumor.
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Objective To prepare quercetin ( QT )-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate ( PLGA-TPGS) nanoparticles ( QPTN) and QT-loaded polylactic-co-glycolic acid ( PLGA) nanoparticles ( QPN) by using QT as model drug and PLGA-TPGS or PLGA as carrier materials, and to investigate the quality of the two nanoparticles. Methods QPTN and QPN were prepared by using the ultrasonic emulsification-solvent evaporation method, and their surface morphology,size and surface charge were detected by using a transmission electron microscope ( TEM) and a Nano ZS90 light scattering and laser Doppler anemometry, respectively. Drug loading ( DL) , entrapment efficiency ( EE) and in vitro drug release of QT in the two nanoparticles were determined by using a reverse phase-high performance liquid chromatography (RP-HPLC) on Hypersil C18 column (4.6 mm×250 mm, 5 μm) with methanol and 0.03% phosphoric acid (3︰2) as mobile phase, and the detective wavelength was 370 nm. Results TEM images exhibited that two nanoparticles were all spherical and regular. The average sizes of QPTN and QPN were (155.4±2.7) nm and (363.8±3.2) nm, while DL and EE of QPTN were approximately (21.6±2.8)%, (93.7±2.9)% (n=6), and DL and EE of QPN were approximately (15.0±1.5)%, (64.6± 1.6)% (n=6), respectively. Both of nanoparticles exhibited sustained release, and the cumulative QT release of QPTN and QPN reached (85.8±2.8)% and (68.6±1.4)% (n=6) at day 30, respectively, with a significant difference between them (P<0.05) . Conclusion QPTN gets smaller size, higher DL and EE, and exhibits sustained release, and the in vitro cumulative QT release is faster and more complete than QPN relatively.
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Objective To prepare quercetin ( QT )-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate ( PLGA-TPGS) nanoparticles ( QPTN) and QT-loaded polylactic-co-glycolic acid ( PLGA) nanoparticles ( QPN) by using QT as model drug and PLGA-TPGS or PLGA as carrier materials, and to investigate the quality of the two nanoparticles. Methods QPTN and QPN were prepared by using the ultrasonic emulsification-solvent evaporation method, and their surface morphology,size and surface charge were detected by using a transmission electron microscope ( TEM) and a Nano ZS90 light scattering and laser Doppler anemometry, respectively. Drug loading ( DL) , entrapment efficiency ( EE) and in vitro drug release of QT in the two nanoparticles were determined by using a reverse phase-high performance liquid chromatography (RP-HPLC) on Hypersil C18 column (4.6 mm×250 mm, 5 μm) with methanol and 0.03% phosphoric acid (3︰2) as mobile phase, and the detective wavelength was 370 nm. Results TEM images exhibited that two nanoparticles were all spherical and regular. The average sizes of QPTN and QPN were (155.4±2.7) nm and (363.8±3.2) nm, while DL and EE of QPTN were approximately (21.6±2.8)%, (93.7±2.9)% (n=6), and DL and EE of QPN were approximately (15.0±1.5)%, (64.6± 1.6)% (n=6), respectively. Both of nanoparticles exhibited sustained release, and the cumulative QT release of QPTN and QPN reached (85.8±2.8)% and (68.6±1.4)% (n=6) at day 30, respectively, with a significant difference between them (P<0.05) . Conclusion QPTN gets smaller size, higher DL and EE, and exhibits sustained release, and the in vitro cumulative QT release is faster and more complete than QPN relatively.
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OBJECTIVE:To study the inhibitory effects of sinomenine(SIN)-loaded polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate(PLGA-TPGS)nanoparticles(SPTN)on the proliferation of HCa-F cells in lymph tubes and ec-topic transplantation tumors in mice. METHODS:HCa-F cell suspension were incubated with normal saline,5-fluorouracil(FS), sinomenine solutions (SS),sinomenine PLGA nanoparticles (SPN) and SPTN,with concentration of 80 μg/ml. The cells were marked with CFSE,and then were injected with suspension 50 μl via one footpad of mice. Inhibitory effect of above suspensions on the proliferation of HCa-F in lymph tubes of mice was observed by fluorescence inverted microscope at 3,6,9,12,24 h(n=15). Mice were divided into normal control group,blank PLGA-TPGS nanoparticles (EPTN) group,normal saline group,SPTN group,SPN group,SS group and FS group with 10 mice in each group. The latter 5 groups were injected with relevant medicine 15 mg/kg,once a day,via tail vein for consecutive 10 days after the model of HCa-F cells-bearing ectopic transplantation tumor mice was established. The serum content of ALT,AST,γ-glutamyltransferase(γ-GT),ALB and T-BIL were determined;solid tu-mors were taken,measured and weighed,and the inhibitory rate of tumor was also calculated. RESULTS:The inhibitory effect of above solution on the proliferation of HCa-F cells in descending order was as follows:SPTN>SPN>FS>SS>normal saline. Com-pared with normal saline group,the serum levels of ALT,AST,γ-GT and TBIL of SPTN group,SPN group,SS group and FS group decreased,while ALB level increased(P<0.05);the amount of tumor volume increase and tumor weight in SPTN group, SPN group and FS group decreased significantly (P<0.05). The inhibitory rate of tumor in 3 groups were 49.62%,40.53% and 33.90%. CONCLUSIONS:SPTN can inhibit the proliferation of HCa-F cells in lymph tubes of mice,and can improve HCa-F cells-bearing ectopic transplantation tumor in mice. It is better than SPN and FS.