ABSTRACT
To improve the solubility of quercetin ( QT) , one of flavonoids that can inhibit the proliferation of vari-ous types of cancer cells, the novel amphiphilic polymer N-( 4-methylimidazole)-hydroxyethyl-chitosan ( MHC) , synthetized by chemical derivatization from chitosan, was used as the self-assembly micelles of QT. The formed polymer was characterized by 1 H NMR, elemental analysis and pyrene fluorescence spectrometry. The formulation of MHC micelles loading quercetin was optimized through single factor experiment. Then the optimized formulation was obtained as follows:the concentration of MHC was 0. 67% and the ratio of drug and carrier was 1 ∶10. The micelles particle size was ( 99. 21 ± 1. 71) nm, Zeta potential was +( 20. 01 ± 0. 72) mV and drug loading was ( 5. 42 ± 0. 32 )%. The in vitro release curve was investigated and was found to conform to Higuchi equation of Q=0. 1101 t1/2 -0. 064. The results of in vivo experiment showed that the mean rentention time and bioavail-ability of the MHC-QT micelles were 21. 42 h and 57. 49 μg h/mL, respectively, compared to 0. 30 h and 2. 50 μg h/mL of the free QT solution. These indicated that the MHC micelles could significantly improve the solubility of QT, the drug sustained-release effect and bioavailability, which would used as carrier for the anti-tumor drugs.
ABSTRACT
OBJECTIVE:To study the targeting of folic acid(FA)-modified docetaxel(DOC)nano-liposome(L-DOC-FA)to hepatocellular carcinoma Bel-7402 cells in vivo and in vitro. METHODS:The cell viability and survival rate of Bel-7402 cells was tested by CCK-8 kit after treated with 0,1,2,5,10 and 20 μg/ml DOC,L-DOC and L-DOC-FA for 24 h. And then,the fluores-cein isothiocyanate was used to label L-DOC and L-DOC-FA nano-liposome,and the rate of L-DOC and L-DOC-FA absorbed by hepatocellular carcinoma Bel-7402 cells were detected. 125I was used to label L-DOC and L-DOC-FA nano-liposome,and then the contents of them in the subcutaneous tumor tissues were detected. 28 Balb/c naked mice were selected and given liver cell suspen-sion via back ih to induce tumor model. After modeling,naked mice were divided into blank control group(normal saline),DOC group(3 mg/kg),L-DOC(3 mg/kg,by DOC)and L-DOC-FA(3 mg/kg,by DOC). They were given relevant medicine intrave-nously once a day for consecutive 30 d. The relative tumor volume in naked mice was detected. RESULTS:DOC,L-DOC and L-DOC-FA all inhibited the cell viability of Bel-7402 cells,the survival rate of cells decreased in concentration-dependant manner;compared with DOC and L-DOC,the cell viability decreased after treated with L-DOC-FA,the survival rate of cells decreased (PL-DOC (31.2%),with statistical significance (P<0.01). The content of L-DOC-FA in tumor was significantly more than that of L-DOC (P<0.01). In addition,3 mg/kg L-DOC-FA showed better inhibitory effect than 3 mg/kg L-DOC and DOC on tumor,and the rela-tive tumor volume was smaller(P<0.01). CONCLUSIONS:L-DOC-FA has obvious targeting to Bel-7402 cells in vivo and in vi-tro,and shows good inhibitory effect on tumor in vivo and in vitro.
ABSTRACT
0.05).The value of J of negative group was(6.180?0.214) ?g?cm-2?h-1,while there was significant difference between trial group and negative group(P