共修饰冰片和叶酸的阿霉素聚酰胺-胺纳米给药系统的制备及体外评价

发布时间：2018-09-10 12:12

【摘要】：本文基于聚酰胺-胺[poly(amido amine),PAMAM G5]树状大分子,通过化学合成叶酸(folic acid,FA)介导的、冰片(borneol,BO)修饰的新型纳米载体(FA-BO-PAMAM),并包载抗癌药物阿霉素(doxorubicin,DOX),以达到增加药物血脑屏障(blood-brain barrier,BBB)的透过性和提高脑胶质瘤靶向性的目的。通过1H NMR验证合成载体的结构,采用透射电镜(TEM)和纳米粒度-电位分析仪(DLS)分别对FA-BO-PAMAM的形貌、粒径和表面电势进行表征;另外基于脑血管内皮细胞(HBMEC)和脑胶质瘤细胞(C6)双细胞模型考察载体的细胞毒性,以及载药复合物体外跨BBB膜转运的能力、细胞摄取效率和体外抗肿瘤的效果。1H NMR的结果表明FA-BO-PAMAM合成成功,在TEM下呈类圆形,大小分布均匀,粒径为(22.28±0.42)nm,zeta电位为(7.6±0.89)m V(n=3)。细胞毒性和体外跨BBB转运实验结果显示,PAMAM功能化修饰冰片显著地降低了PAMAM毒性,提高了生物安全性,同时增加了载药复合物跨BBB转运率。细胞摄取和体外抗肿瘤实验结果表明,叶酸的修饰增加了C6细胞对载药复合物的总摄取量,且提高了体外对C6细胞的抑制率。因此,该新型靶向纳米载体增加了药物在肿瘤部位的蓄积量,显示了其在治疗脑胶质瘤应用中的潜能。
[Abstract]:Based on the dendritic macromolecules of poly (amido amine) (poly (amido amine) PamAM-G5, folic acid (folic acid,FA) -mediated synthesis was carried out in this paper. Borneol (borneol,BO) modified novel nano-carrier (FA-BO-PAMAM) was coated with adriamycin (doxorubicin,DOX) to enhance the permeability of blood-brain barrier (blood-brain barrier,BBB) and the targeting of glioma. The structure of the synthesized support was verified by 1H NMR. The morphology, particle size and surface potential of FA-BO-PAMAM were characterized by transmission electron microscope (TEM) (TEM) and nanocrystalline grain-potential analyzer (DLS). In addition, the cytotoxicity of the vector and the ability of the drug carrier complex to transport through the BBB membrane in vitro were investigated based on the dual cell models of (HBMEC) and C6 cells of cerebrovascular endothelial cells. The results of cell uptake efficiency and in vitro anti-tumor effect. 1H NMR showed that FA-BO-PAMAM was synthesized successfully. The FA-BO-PAMAM was round and uniform in size and size under TEM, and its particle size was (22.28 卤0.42) nm,zeta potential was (7.6 卤0.89) m V (nm3). The results of cytotoxicity and in vitro translocation of BBB showed that Pam functionalized borneol significantly decreased the toxicity of PAMAM, improved the biosafety and increased the translocation rate of BBB. The results of cell uptake and in vitro antitumor experiments showed that folic acid modification increased the total uptake of C6 cells and the inhibition rate of C6 cells in vitro. Therefore, the novel targeted nanoparticles increase the accumulation of drugs in tumor sites and show their potential in the treatment of glioma.
【作者单位】：浙江中医药大学药学院;
【基金】：国家自然科学基金资助项目(81274089,81473361) 浙江省自然科学基金资助项目(LZ13H280001,LY12H280004) 浙江省科技创新团队资助项目(2010R500445)
【分类号】：R943

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