Anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes / 药学学报

The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L was prepared by organic solvent injection method. Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.

Preparation and in vitro properties of folate receptor targeting docetaxel-loaded amphiphilic copolymer-modified liposomes / 药学学报

A novel amphiphilic copolymer, folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized as liposomal modifying material with folate receptor targeting and long circulating property. FA-PEG-PCHL-modified docetaxel-loaded liposomes (FA-PDCT-L) were prepared by organic solvent injection method, and the system was optimized using central composite design-response surface methodology. The structure of the FA-PEG-PCHL copolymer was confirmed by FT-IR and 1H NMR. Ultrafiltration technique, transmission electron microscope, dynamic light scattering and electrophoretic light scattering, and fluorescence polarization method were used to study the physicochemical parameters of FA-PDCT-L. FA-PDCT-L showed spherical or ellipsoid shape. The mean particle sizes were in the range of 111.6-126.9 nm, zeta potentials were from -6.54 mV to -14.13 mV and the drug encapsulation efficiency achieved 97.8%. The observed values agreed well with model predicted values. The membrane fluidity increased with the increment of the molecular weight of PEG and the decrement of the amount of FA-PEG-PCHL. The in vitro release test showed that the drug could be sustained-released from liposomes without a burst release and with stability for 6 months. After 24 h only 31.1%, 27.2% and 19.5% of encapsulated docetaxel were released for FA-PDCT10000-L, FA-PDCT4000-L and FA-PDCT2000-L, respectively. This work is useful for further research on the application of the synthesized copolymer-modified long circulating liposomes for cancer therapy.

Preparation and characterization of oxaliplatin-loaded nanostructured lipid carriers / 药学学报

Oxaliplatin-loaded nanostuctured lipid carriers (OP-NLC) were prepared by ultrasonic emulsification method. And its optimal prescription was selected by orthogonal design. The laser light scattering technique, zeta potential analyzer, TEM, DSC, XRD and HPLC were employed to study the physicochemical parameters of OP-NLC, which displayed in terms of particle size, zeta potential, crystalline, drug loading and encapsulation efficiency. The results showed that OP-NLC had an average diameter of (111 +/- 20) nm, zeta potential of (-27.4 +/- 13.1) mV, encapsulation efficiency of (77.4 +/- 2.5) % and drug content of (0.8 +/- 1.5) mg mL(-1). TEM, DSC and XRD indicated that OP-NLC was spherical and the drug was dispersed as nanoparticles by means of non-crystalline. The in vitro release test showed that the drug could be sustained-released from NLC in buffer solution (pH 4.5) after a burst release in initial phase.