目的 制备紫杉醇/油酰壳聚糖纳米粒(PTX/OCS-NPs),并考察其理化特性及肺急性毒性。方法 以油酰壳聚糖(OCS)为载体制备了PTX/OCS-NPs,并通过透射电子显微镜(TEM)、动态光散射(DLS)、高效液相色谱法(HPLC)、动态透析法等表征及检测纳米粒的结构、形态、粒径、粒度分布、载药量、包封率、体外释放、毒性等理化特性。结果 PTX/OCS-NPs的形态呈类球形,分散均匀;纳米粒的粒径为(292.4±20)nm,多分散性指数(PDI)为0.246,Zeta电位在+25 mV左右。制备的PTX/OCS-NPs载药量为15.06%,包封率48.96%,在磷酸缓冲液(PBS,pH 7.4和pH 4.5)中具有缓释功能(48 h的累计释放量分别为41.41%和56.23%)。小鼠肺急性毒性显示,血液中白细胞数量在正常范围内,病理HE染色结果显示制备的载药纳米粒对肺组织、黏膜、肺泡等结构均无损伤,无间质增生、无炎症细胞浸润,表明载药系统具有很好的生物安全性和生物相容性。结论 紫杉醇/油酰壳聚糖纳米粒具有优良的理化特性,载药量高,具有缓释作用,无肺部急性毒性,有望成为输送紫杉醇等难溶性抗癌药物的良好递药系统。
Abstract
OBJECTIVE To prepare paclitaxel / oleyl chitosan nanoparticles (PTX / OCS-NPs) and to examine its physicochemical properties and acute lung toxicity. METHODS The morphology and size were determined by transmission electron microscope (TEM). The average diameters and polydispersity index were evaluated by dynamic light scattering (DLS). Encapsulation efficiency (EE) and in vitro release were determined by high performance liquid chromatography (HPLC). RESULTS The RESULTS of PTX/OCS-NPs were spherical in shape, uniform particle size and dispersed uniformly. The diameters of NPs were(292.4±20)nm, PDI less than 0.246 and Zeta potential was about 25 mV. The drug loading of PTX was 15.06%. The encapsulation efficiency of PTX was 48.96%. In vitro release study showed that the cumulative release of PTX from NPs were 41.41% and 56.23% respectively, within 48 h in phosphate buffered saline (PBS) pH 7.4 and pH 4.5. Acute toxicity showed that there was no change in the number of white blood cells in the blood, and the content of LDH in the bronchoalveolar lavage fluid was not changed. The RESULTS indicated that the drug delivery system has a good biosafety and biocompatibility. CONCLUSION PTX / OCS-NPs have excellent physicochemical properties, high drug loading, with sustained release, no acute lung toxicity, that is expected to be a good delivery of paclitaxel and other difficult anti-cancer drug delivery system.
关键词
紫杉醇 /
油酰壳聚糖 /
理化特性 /
肺部急性毒性 /
纳米粒
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Key words
paclitaxel /
oleyl-chitosan /
physicochemical property /
acute lung toxicit /
nanoparticles
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中图分类号：
R944
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参考文献
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基金
国家自然科学基金项目资助(81774125); 国家科技部科技计划项目资助(2013GA740103); 山东省自然科学基金资助(ZR2012CM025)
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