载10-羟基喜树碱液态氟碳纳米粒制备及其表征、体外增强超声显像效果观察

Preparation of 10-HCPT loaded perfluoropentane nanoparticles and observation its characteristic,enhancement effect for ultrasound imaging in vitro

目的研制一种包裹液态氟碳(PFP)的新型载药纳米级超声造影剂,考察其基本特性并观察其体外增强超声显像效果。方法采用旋转蒸发和探头超声法制备载10-羟基喜树碱(10-HCPT)的液态氟碳(PFP)纳米粒,在光学显微镜和透射电镜下观察纳米粒形态,采用马尔文仪测量纳米粒粒径和电荷。采用紫外分光光度计测定纳米粒包封率,并应用低强度聚焦超声(LIFU)辐照载药液态氟碳纳米粒溶液,观察纳米粒相变情况及其增强超声显像效果。结果制备的载药脂质纳米粒外观为乳白色混悬液,在油镜及透射电镜下观察,载药纳米粒形态规则,分布均一,平均粒径约(500.82±25.97)nm,表面平均电位为(-47.77±3.09)mV;在体外经LIFU辐照后,可见纳米粒发生液气相变形成微泡,在基波模式和谐波模式下,均可显著增强超声显影。结论成功研制了包裹液态氟碳的载药脂质纳米粒,可望成为一种新型的多功能超声造影剂。

Objective To prepare a novel drug-loaded nano-scale ultrasound contrast agent and observe its enhancement effect for ultrasound imaging in vitro.Methods The 10-Hydroxy camptothecin（10-HCPT）loaded perfluoropentane（PFP）nanoparticles were prepared with rotary evaporator and probe-type sonication methods.The morphology and structure of nanoparticles were observed by optical microscope and transmission electron microscope（TEM）.The mean diameter and charge of the nanoparticles were measured by Malvern instrument.The entrapment efficiency was determined by ultraviolet spectrophotometer.The emulsion of drug-loaded nanoparticles were sonicated by low intensity focused ultrasound（LIFU）,the phase-shift result and enhancement effect for ultrasound imaging were then observed.Results The drugloaded nanoparticles appeared as milk white suspension,showed uniform size and regular shape under the microscope and TEM.The mean diameter and charge were（500.82±25.97）nm and（-47.77±3.09）mV,respectively.After sonicating by LIFU,nanoparticles changed phase and transformed into microbubbles was found under the microscope.The ultrasound imaging of nanoparticle suspension was significantly enhanced both under the fundamental mode and harmonic mode.Conclusion The 10-HCPT loaded perfluoropentane nanoparticles are successfully prepared and would become a novel kind of multifunctional ultrasound contrast agent.