奈妥吡坦-聚乙二醇聚乳酸共聚物纳米粒的制备与表征
Preparation and Characterization of Netupitant-loaded mPEG-PDLLA Nanoparticles
-
摘要:目的 采用聚乙二醇聚乳酸嵌段共聚物(mPEG-PDLLA)提高奈妥吡坦(netupitant)的水溶性,为开发获得一种奈妥吡坦注射液提供实验基础。方法 采用薄膜水化法制备包载奈妥吡坦的mPEG-PDLLA纳米粒(NT/mPEG-PDLLA-NPs),以载药量和粒径为指标,通过单因素考察优化处方(奈妥吡坦与mPEG-PDLLA的药质比)和工艺(成膜温度和时间)。采用激光散射粒度仪和透射电子显微镜对NT/mPEG-PDLLA-NPs的粒径、电位、形态进行表征,采用MTT法对纳米粒的细胞毒性进行表征。结果 NT/mPEG-PDLLA-NPs的最佳处方和工艺为:奈妥吡坦与mPEG-PDLLA药质比为1:6, 成膜温度为55 ℃, 成膜时间为30 min。此条件下制备得到的NT-mPEG-PDLLA-NPs呈淡蓝色透明液体,载药量为14%,药物质量浓度高达10 mg/mL,平均粒径58 nm,电位-0.29 mV,电镜下观察纳米粒呈球形或类球形颗粒,药物包载未显著改变奈妥吡坦的细胞毒性。结论 成功制备了NT/mPEG-PDLLA-NPs,显著提高了奈妥吡坦的水溶性(10 mg/mL),为开发奈妥吡坦的可注射制剂提供了潜在可行的方法。Abstract:Objective Methoxy poly (ethylene glycol)-poly (lactic acid) (mPEG-PDLLA) was used to increase water solubility of netupitant, thus to provide the experimental basis for development of the injection of netupitant.Methods Film hydration method was ultilized to prepare the netupitant-loaded mPEG-PDLLA nanoparticles (NT/mPEG-PDLLA-NPs). The preparation formulation and technology were optimized based on the single factor tests by investigating the effect of netupitant/mPEG-PDLLA mass ratio (m/m), filming temperature and time on the mean particle diameters and loading capacities. The size distributions and Zeta potentials of NT/mPEG-PDLLA-NPs were investigated using dynamic light scattering analysis, and the morphology was observed under the transmission electron microscope (TEM). The cytotoxicity of NT/mPEG-PDLLA-NPs evaluated by MTT method.Results The optimal NT/mPEG-PDLLA-NPs were achieved at the netupitant/mPEG-PDLLA mass ratio of 1/6 with filming temperature at 55 ℃ and filming time for 30 min. The resulting NT/mPEG-PDLLA-NPs displayed an opalescent and translucent appearance, with a high loading capacity of 14% and netupitant concentration of 10 mg/mL. NT/mPEG-PDLLA-NPs showed a spherical morphology, with a mean diameter of 58 nm and a nearly neutral Zeta potential of -0.29 mV. The NT/mPEG-PDLLA-NPs showed a cytotoxicity similar to free NT.Conclusion Netupitant was successfully loaded into mPEG-PDLLA-NPs to significantly increased the water solubility, thus providing the experimental foundation for the further development of injection of netupitant.
© 2019 《四川大学学报(医学版)》编辑部 版权所有
开放获取 本文遵循知识共享署名—非商业性使用4.0国际许可协议(CC BY-NC 4.0),允许第三方对本刊发表的论文自由共享(即在任何媒介以任何形式复制、发行原文)、演绎(即修改、转换或以原文为基础进行创作),必须给出适当的署名,提供指向本文许可协议的链接,同时标明是否对原文作了修改;不得将本文用于商业目的。CC BY-NC 4.0许可协议详情请访问 https://creativecommons.org/licenses/by-nc/4.0