Study On Inhibitory Effect Of Encapsulated Apatinib Nano Micelles Against Human Umbilical Vascular Endothelial Cells

Objectives: Apatinib,a small molecular inhibitor which has an anti-advanced gastric cancer effect,can significantly improve survival of patients who suffer advanced gastric cancer,but its side effects may exert a limited influence on treatment of advanced gastric cancer.Nano drug-loaded systems have features of biological safety,targeting and sustained drug release and can be used to improve the dosage forms of Apatinib.In this study,nano micelle m PEG5000-b-PCL5000-Apatinib was synthesized and its features and inhibitory effects on human umbilical vascular endothelial cells(HUVECs)were evaluated.Methods: MPEG5000-b-PCL was synthesized by a ring-opening polymerization with m PEG5000 as an initial molecule and was characterized by H1 NMR,FT IR and GPC.MPEG5000-b-PCL5000-Apatinib was synthesized by dialysis method and its diameter,shape,drug loading rate and encapsulation efficiency were determined by Dynamic Light Scattering,Transmission Electron Microscope and Ultraviolet Spectrophotometer respectively.For m PEG5000-b-PCL5000-Apatinib,its sustained release effect was evaluated in vitro and its biological safety was assessed by inhibitory assay of nano micelle without Apatinib on proliferation of HUVECs and hemolysis test.Inhibitory on proliferation,migration,tube formation of HUVECs by m PEG5000-b-PCL5000-Apatinib was evaluated by CCK-8 assay,transwell assay,tube formation assay and fluorescent uptake experiments.Results: MPEG5000-b-PCL5000-Apatinib was successfully synthesized with mean diameter size of 55.7nm,PDI of 0.068 which indicates a near mono-dispersed system and with a spherical shape.Its drug loading rate and encapsulation efficiency were shown to have,respectively,a positive and negative correlation with dose ratio of m PEG5000-b-PCL5000 and Apatinib.Hemolytic test and inhibitory assay of nano micelle without Apatinib prove biological safety of m PEG5000-b-PCL5000-Apatinib.MPEG5000-b-PCL5000-Apatinib released Apatinib slowly in vitro,and the rate reached 62.9% after 72 h.The inhibitory effect of m PEG5000-b-PCL5000-Apatinib determined by CCK 8 assay,transwell assay,tube formation assay and fluorescent uptake experiments possesses features of concentration-dependence and released time dependence.When releasing over 3 days,Apatinib encapsulated nano micelles would surpass free Apatinib on inhibitory against HUVECs.Conclusion: Apatinib encapsulated nano micelle was successfully synthesized with quite excellent sustained release effect,biological safety and stable inhibitory effect.Encapsulating Apatinib into a nano drug-loaded system such as m PEG5000-b-PCL5000-Apatinib owns a good feasibility with high advantages.