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目的:探讨载阿帕替尼(apatinib)纳米胶束对脐静脉内皮细胞(HUVECs)的抑制作用及其释放规律与安全性。方法:分别用紫外-吸收法和溶血实验检测载apatinib纳米胶束的释放率与使用安全性,然后分别用CCK-8实验、迁移实验、体外小管形成实验观察载apatinib纳米胶束对HUVECs的抑制作用。结果:载apatinib纳米胶束有短暂的突释效应(2 h达20.5%),随后呈缓慢释放(72 h达62.9%),其溶血实验阴性。载apatinib纳米胶束与单纯apatinib均能明显抑制HUVECs的增殖,并呈浓度与时间依赖性(均P<0.05);48 h内载apatinib纳米胶束对HUVECs的抑制率小于单纯apatinib组(48 h IC50:1.385μmol/L vs.0.768μmol/L,P=0.012),但随着时间延长至72 h,载apatinib纳米胶束的抑制率超过单纯apatinib(63.34%vs.59.70%,P=0.005)。载apatinib纳米胶束与单纯apatinib均能明显抑制HUVECs的迁移及小管形成,并呈浓度与释放时间依赖性,且体外释放3 d的载apatinib纳米胶束对HUVECs迁移及成管的抑制超过单纯apatinib(均P<0.05)。结论:载apatinib纳米胶束具备良好的安全性及缓释性,对apatinib进行纳米包载可增强apatinib对HUVECs的抑制作用并延长apatinib的作用时间窗。
OBJECTIVE: To investigate the inhibitory effect, release and safety of apatinib nanomicelles on human umbilical vein endothelial cells (HUVECs). Methods: The release rate and safety of apatombicamycin-loaded nanomicelles were detected by UV-Absorption and hemolysis tests respectively. The inhibitory effect of apatinib nanomicelles on HUVECs was evaluated by CCK-8 assay, migration assay and in vitro tubular formation assay effect. RESULTS: Apatombib nanomicelles contained a transient burst effect (20.5% at 2 h), followed by a slow release (62.9% at 72 h). The hemolytic assay was negative. Both apatinib and apatinib significantly inhibited the proliferation of HUVECs in a concentration-dependent manner (all P <0.05). The inhibition rate of apatinib nanomicelles on HUVECs after 48 h was lower than that of apatinib alone (48 h IC50: 1.385μmol / L vs0.768μmol / L, P = 0.012). However, the inhibitory rate of apatinib-loaded nanomicelles was longer than that of apatinib alone (63.34% vs.59.70%, P = 0.005) . Both apatinib and apatinib could significantly inhibit the migration and tubular formation of HUVECs in a time-dependent and time-dependent manner. The release of apatinib nanomicelles in vitro for 3 days inhibited the migration and tube formation of HUVECs more than that of apatinib (All P <0.05). CONCLUSION: The apatinib nanomicelles possess good safety and sustained release properties. Nanoparticle apatinib can enhance the inhibitory effect of apatinib on HUVECs and prolong the time window of apatinib.