甘草次酸修饰多西紫杉醇磁性纳米粒的制备与表征

Preparation and Characterization of Glycyrrhetinic Acid-modified Docetaxel Magnetic Nanoparticles

目的:制备甘草次酸修饰多西紫杉醇磁性纳米粒(GA-DTX-NGO/IONP-NPs),并对其理化性质进行评价。方法:以磁性纳米氧化石墨烯(NGO/IONP)作为抗肿瘤药物载体,多西紫杉醇(DTX)为模型药物,甘草次酸(GA)为靶头分子。采用水热法合成NGO/IONP、酰胺化反应合成GA修饰的壳聚糖(GA-CS)后,采用傅里叶红外光谱法、差示扫描量热法及振动样品磁测量法等对两者进行表征。采用离子凝胶化法制备GA-DTX-NGO/IONP-NPs;采用透射电镜、纳米粒度分析仪等对其微观形态、粒径及Zeta电位进行观察和测定;采用超滤离心法测定其包封率和载药量;通过观察有无外加磁场时的状态考察其磁性;结合808 nm激光对其进行光热转换试验。结果:成功合成了NGO/IONP和GA-CS,且NGO/IONP呈现超顺磁性。GA-DTX-NGO/IONP-NPs在透射电镜下呈圆球状,粒径为(262.8±4.23)nm,Zeta电位为(13.6±1.51)mV,包封率为(94.29±0.50)%,载药量为(17.12±0.12)%。GA-DTX-NGO/IONP-NPs的外观呈黑色,分散均匀;其在外加磁场下磁性纳米粒可定向移动,显示出良好的磁定向性。在808 nm激光照射下,GA-DTX-NGO/IONP-NPs具有良好的光热转换效应,且呈浓度和时间依赖趋势。结论:本研究成功制备了一种磁性纳米载药系统GA-DTX-NGO/IONP-NPs,可为肿瘤的磁热-化疗联合治疗提供一定的理论依据。

OBJECTIVE:To prepare Glycyrrhetinic acid-modified docetaxel magnetic nanoparticles(GA-DTX-NGO/IONPNPs),and to evaluate its physicochemical properties.METHODS:Magnetic nano graphene oxide(NGO/IONP)was chosen as the anti-tumor drug carrier,docetaxel(DTX)as the model drug and glycyrrhetinic acid(GA)as the target molecule.Firstly,NGO/IONP was synthesized by hydrothermal method and GA-CS was synthesized by amidation reaction.Fourier IR spectrometer,DSC and vibration sample magnetic measuring instrument were used to characterize NGO/IONP and GA-CS.GA-DTX-NGO/IONP-NPs were prepared by the ion gelation method.TEM and particle size analyzer were used to observe and determine the morphology,particle size and Zeta potential of GA-DTX-NGO/IONP-NPs;the ultrafiltration-centrifugation method was used to determine encapsulation efficiency and drug loading amount;the magnetic properties were investigated by investigating the state with or without external magnetic field;the photothermal conversion test was carried out with laser irradiation of 808 nm.RESULTS:NGO/IONP and GA-CS were successfully synthesized,and NGO/IONP exhibited superparamagnetism characteristics.GA-DTX-NGO/IONP-NPs were spherical under TEM,the particle size was(262.8±4.23)nm and the Zeta potential was(13.6±1.51)mV.The encapsulation rate and drug loading amount were(94.29±0.50)%and(17.12±0.12)%,respectively.GA-DTX-NGO/IONP-NPs were black in appearance and evenly dispersed.Under the external magnetic field,the magnetic nanoparticles could move directionally,showing good magnetic properties.GA-DTX-NGO/IONP-NPs showed a good concentration-and time-dependent photothermal conversion effect under 808 nm laser irradiation.CONCLUSIONS:GA-DTX-NGO/IONP-NPs are successfully prepared.This study could provide some theoretical basis for the combined treatment of magnetic heating-chemotherapy for liver tumors.