3.6纳米粒载药量和包封率.doc

PLGA-PLL-PEG纳米粒的制备 药学院 浦药剂1005 吉冬悦 林丽 洪峰 赵星龙 摘 要: 本课题选用可生物降解材料聚乳酸羟基乙酸（PLGA）、聚赖氨酸（PLL）、聚乙二醇（PEG）作为合成新型纳米载药系统的原料，通过优化反应条件，制得PLGA-PLL-PEG聚合物。采用该聚合物包载抗白血病经典药物柔红霉素（DNR）及第三代MDR逆转剂汉防己甲素（Tet），并偶联转铁蛋白（Tf），构建一种具有主动靶向性能的Tf-PEG-PLL-PLGA纳米粒，以期逆转白血病多药耐药。本课题具体研究内容与结果如下：选用复乳化溶剂挥发法制备共载DNR和Tet的PLGA-PLL-PEG纳米粒，优化工艺条件并交联Tf，其平均粒径为213.0±12nm，PI值为0.075，zeta电位为-19.16mv，外观规则圆形。纳米粒中DNR载药量为3.63±0.15%，包封率为70.23±1.91%，Tet载药量为4.27±0.12%，包封率为86.5±0.7%，Tf含量为2.18±0.11%（w/w）。 关键字：载药纳米粒子；制备工艺；溶剂扩散法； 复乳化溶剂挥发法；转铁蛋白 In our research, we use the biodegradable materials including poly(lactic-co-glycolic acid) (PLGA), poly-L-lysine (PLL), polyethylene glycol (PEG) to synthesis novel nanodrug carrier system. We optimize the reaction conditions to synthesis PLGA-PLL-PEG, then use it to delivery the classical antileukemic drug daunorubicin (DNR) and the MDR reversal agents of tetrandrine (Tet) and couple transferrin (Tf).We except the Tf-PEG-PLL-PLGA nanoparticles can overcome the problem of multidrug resistance of leukemia. The main research contents and results are as follows. We chose double-emulsion method to prepare Tf-DNR/Tet-loaded PLGA-PLL-PEG nanoparticle through optimizing process conditions and cross-linking Tf. Nanoparticle was regular roundness, it’s average size was 213.0 ± 12 nm with polydisperse index (PI) of 0.075, and the zeta potential was -19.16 mv. The drug loading of nanoparticles DNR was 3.63 ± 0.15%, encapsulation efficiency was 70.23 ± 1.91%. The drug loading of Tet was 4.27 ± 0.12%, the encapsulation efficiency was 86.5 ± 0.7%, the concentration of transferrin was 2.18 ± 0.11%(w/w). Keywords: drug-loaded nanoparticles; preparation process; solvent diffusion method; double emulsion solvent evaporation method; transferrin 1、研究背景 药物纳米化可能会使得一些难溶有机化合物用作药物，这将使目前用于医药的合成化学物质数量增加。用纳米粒子作为药物载体可实现靶向输送、缓释给药的目的，这是因为小粒子可以进入很多大粒子难以进入的人体器官组织，如小于50nm的粒子就能穿过肝脏内皮或通过淋巴传送到脾和骨髓，也可能到达肿瘤组织。此外纳米粒子还能够越过许多生物屏障到达病灶部位，如透过血脑屏障把药物送到脑部，通过口服给药可使药物在淋巴结中富集等。而具有生物活性的大分子药物（如蛋白类，多肽药物等）就很难越过生物屏障，用纳米粒子作为载体可克服这一困难，并提