溶酶体酸性微环境敏感型粒径可变纳米粒的构建及评价
Construction and evaluation of lysosomal acidic microenvironment-sensitive size-variable nanoparticle
作者：邰晓伟;王蛘;高会乐;何勤;
Author：
收稿日期： 年卷（期）页码：2017,32(04):-353-356
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：粒径变化;支化聚乙烯亚胺;电荷翻转;内涵-溶酶体;溶酶体酸敏感;阿霉素;纳米粒;黑色素瘤
Key words：
基金项目：
中文摘要
目的构建一种以功能性支化聚乙烯亚胺(b PEI)为基本骨架材料的粒径可变纳米粒,用于递送药物至黑色素瘤的深部区域。方法通过酰胺键修饰特定量的琥珀酸酐至b PEI骨架上,得到具有电荷翻转功能的材料NSP,再引入聚N-异丙基丙烯酰胺(PNIPAM)制备粒径可变纳米粒(PSP),分别考察其粒径、Zeta电位和释药行为;考察B16F10细胞对PSP的摄取及胞内内涵-溶酶体对PSP的影响;通过构建体外三维肿瘤球模型来考察纳米粒的穿透能力。结果载阿霉素粒径可变纳米粒(D/PSP)在p H7.4缓冲液中的粒径、PDI和Zeta电位分别为31.2±4.8 nm、0.106±0.015、-2.26±0.06 m V。在内涵-溶酶体所对应的p H5.0条件下,D/PSP的粒径可膨胀至891.6±26.3 nm,PDI为0.256±0.123,Zeta电位为15.61±0.19 m V。B16F10细胞对D/PSP的摄取在一定范围内呈孵育浓度依赖性及时间依赖性,其主要的入胞机制为网格蛋白介导和能量依赖型的内吞途径。结论成功制备了具有较好的溶酶体酸性微环境响应性的PSP,D/PSP具有较强的肿瘤球穿透能力。
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