Preparation and in vitro anticancer activity of DOX-VES-loaded copolymer micelles / 中国药学杂志

ABSTRACT

OBJECTIVE: To enhance the anticancer activity of doxorubicin(DOX) by conjugating DOX and vitamin E succinate (VES) and loading the conjugate into hyaluronic acid-octadecylamine (HA-C18) copolymer micelles. METHODS: DOX and VES were conjugated by amide reaction. DOX-VES/HA-C18micelles were prepared via a probe-type ultrasonication technique. The morphology of the micelles was determined using a transmission electron microscopy (TEM).Dynamic light scattering (DLS) technique was used to determine the particle size distribution, hydrodynamic diameters, and stability of the micelles. Ultracentrifugation was exploited for measuring the drug loading (DL) and encapsulation efficiency (EE), and the in vitro release was investigated using a dialysis tubing. The cellular uptake and cellular distribution of drug-loaded micelles in MCF-7 cells were observed by fluorescence microscope, and the fluorescence intensity of DOX was evaluated by flow cytometer. The cytotoxicity of free DOX and drug-loaded micelles was tested by MTT assay against MCF-7 cells. RESULTS: DOX-VES/HA-C18 showed a nearly spherical morphology and good stability in PBS (pH 7.4) and 10% FBS. The particle size and zeta potential were (184.6±9.42) nm and (-20.7±1.23) mV, respectively. The DL and EE were (15.8±2.85)% and (94.2±1.32)%, respectively. DOX-VES/HA-C18had a good controlled drug release property. Furthermore, DOX-VES/HA-C18with accumulation in nucleipresented higher anti-tumor activity than free DOX and DOX/HA-C18. CONCLUSION: DOX-VES conjugate has synergistic anti-tumor effect and good application prospects.