基于聚（γ-谷氨酸-co-L-丙交酯）-1,2-二月桂酰基-sn-甘油-3-磷酸乙醇胺两亲性共聚物的纳米粒子的构建及其作为潜在药物传递载体的研究。
Construction of nanoparticles based on amphiphilic copolymers of poly(γ-glutamic acid co-L-lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine as a potential drug delivery carrier.
机构信息
National Center for Nanoscience and Technology, Laboratory of Nanobiomedicine and Nanosafety, Division of Nanomedicine and Nanobiology, No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China; School of Basic Medical Sciences of Jiamusi University, Jiamusi 154000, China; The First Affiliated Hospital of Jiamusi University, Jiamusi 154002, China.
出版信息
J Colloid Interface Sci. 2014 Jan 1;413:54-64. doi: 10.1016/j.jcis.2013.09.022. Epub 2013 Sep 21.
A novel amphiphilic copolymer (γ-PGA-co-PLA-DPPE) containing poly(γ-glutamic acid) (γ-PGA), polylactide (PLA), and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) segments has been successfully synthesized. The chemical structures of the copolymers were characterized by Fourier-transform infrared spectroscopy (FT-IR), NMR ((1)H NMR, (13)C NMR, (31)P NMR), and thermogravimetric analysis (TGA). In order to estimate the feasibility as novel drug carriers, an anti-tumor model drug, doxorubicin hydrochloride salt (DOX) was encapsulated into the copolymers nanoparticles (NPs) by double emulsion and nanoprecipitation methods. The influence of processing factors on encapsulation efficiency and particle size using double emulsion and nanoprecipitation technique were studied. In addition, the DOX-loaded NPs exhibited pH-dependent drug release profiles in vitro. The cumulative release of DOX-loaded NPs was much faster at pH 5.0 than that at pH 7.4. In vitro cytotoxicity test of DOX-loaded NPs against Hela and C666-1 cells demonstrated that DOX-loaded NPs exhibited effectively time-delayed cytotoxicity. Confocal laser scanning microscopy (CLSM) showed that DOX-loaded NPs accumulated mostly in lysosomes instead of cell nucleus, in contrast to free DOX. Therefore, the copolymer nanoparticles were proved to be an available carrier for anti-tumor drug delivery.
一种新型两亲性共聚物（γ-PGA-co-PLA-DPPE），含有聚（γ-谷氨酸）（γ-PGA）、聚乳酸（PLA）和 1,2-二月桂酰基-sn-甘油-3-磷酸乙醇胺（DPPE）片段，已成功合成。通过傅里叶变换红外光谱（FT-IR）、核磁共振（1H NMR、13C NMR、31P NMR）和热重分析（TGA）对共聚物的化学结构进行了表征。为了评估其作为新型药物载体的可行性，将抗肿瘤模型药物盐酸阿霉素（DOX）包裹在共聚物纳米粒子（NPs）中，采用双重乳液和纳米沉淀法。研究了双重乳液和纳米沉淀技术中加工因素对包封效率和粒径的影响。此外，载 DOX 的 NPs 在体外表现出 pH 依赖性药物释放特性。在 pH 5.0 时，载 DOX 的 NPs 的累积释放速度明显快于在 pH 7.4 时的释放速度。载 DOX 的 NPs 对 Hela 和 C666-1 细胞的体外细胞毒性试验表明，载 DOX 的 NPs 表现出有效的时滞细胞毒性。共聚焦激光扫描显微镜（CLSM）显示，与游离 DOX 相比，载 DOX 的 NPs 主要积聚在溶酶体中，而不是细胞核中。因此，共聚物纳米粒子被证明是一种有效的抗肿瘤药物载体。
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