9-NC-loaded folate-conjugated polymer micelles as tumor targeted drug delivery system: Preparation and evaluation in vitro
9-NC-loaded folate-conjugated polymer micelles as tumor targeted drug delivery system: Preparation and evaluation in vitro
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负载9-NC的叶酸共轭聚合物胶束作为肿瘤靶向药物递送系统：体外制备和评价
DOI：
10.1016/j.ijpharm.2008.12.035
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发表时间：
2009-05-08
影响因子：
5.8
通讯作者：
Lu, WeiYue
中科院分区：
文献类型：
--
作者：
Han, Xue;Liu, Jing;Lu, WeiYue
本研究以叶酸-聚乙二醇-二硬脂酰磷脂酰乙醇胺（FA-PEG-DSPE）和甲氧基-聚乙二醇-二硬脂酰磷脂酰乙醇胺（MPEG-DSPE）为原料，制备了叶酸-聚乙二醇-二硬脂酰磷脂酰乙醇胺（FA-PEG-DSPE）聚合物胶束，并将其用于包裹抗癌药物9-硝基喜树碱（9-NC）。通过共聚物的临界胶束化浓度（CMC）值、胶束粒径、Zeta-电位、包封率和载药率来表征制剂。选择FA-PEG-DSPE和MPEG-DSPE的摩尔比以避免巨噬细胞，同时表达高活性靶向能力。研究了叶酸偶联聚合物胶束对3种肿瘤细胞株（HeLa、SGC 7901和BXPC 3）的靶向性。采用四甲基偶氮唑盐（MTT）法评价叶酸偶联聚合物胶束的体外药效。结果表明，MPEG-DSPE和FA-PEG-DSPE的CMC值分别为0.97 × 10（-5）M和1.0 × 10（-5）M。叶酸偶联胶束的平均粒径为21-24 nm，空胶束和载药胶束的粒径分布均较窄。包封率和载药量分别为97.6%和4.64%。载药胶束在4 ℃下储存4周期间是稳定的。胶束保持相似的尺寸，并且没有显示9-NC泄漏。叶酸偶联胶束中FA-PEG-DSPE和MPEG-DSPE的最佳摩尔比为1：100，能有效增溶9-NC，且在体外能避开巨噬细胞，抗肿瘤活性高于MPEG-DSPE载药胶束和游离抗癌药物。叶酸偶联聚合物胶束可避开巨噬细胞，是一种很有前途的难溶性抗癌药物载体，可通过叶酸受体介导内吞作用靶向肿瘤细胞。(c)2009 Elsevier B. V.保留所有权利。
In this study, folate-conjugated polymer micelles were synthesized by mixing folate-poly(ethylene glycol)-distearoylphosphatidylethanolamine (FA-PEG-DSPE) and methoxy-poly(ethylene glycol)-distearoylphosphatidylethanolamine (MPEG-DSPE) to encapsulate anticancer agent 9-nitro-camptothecin (9-NC). Formulations were characterized by critical micellization concentration (CMC) values of copolymers, micelle particle size, zeta-potential, encapsulation efficiency and drug loading efficiency. The molar ratio of FA-PEG-DSPE and MPEG-DSPE was chosen to avoid the macrophages and at the same time express highly active targeting ability. The targeting ability of folate-conjugated polymer micelles was investigated against three kinds of tumor cell lines (HeLa, SGC7901 and BXPC3). The drug efficacy in vitro of folate-conjugated polymer micelles was evaluated by using the methylthiazoletetrazolium (MTT) method. The results showed that the CMC values of MPEG-DSPE and FA-PEG-DSPE were 0.97 x 10(-5) M and 1.0 x 10(-5) M, respectively. The average size of folate-conjugated micelle was about 21-24 nm and the micelle size distribution of both empty and drug-loaded micelles were rather narrow. The encapsulation efficiency and drug loading efficiency were 97.6% and 4.64%, respectively. The drug-loaded micelles were stable during storage at 4 degrees C for 4 weeks. Micelles maintain the similar size and did not show 9-NC leakage. The best molar ratio of FA-PEG-DSPE and MPEG-DSPE in folate-conjugated micelles was 1:100 which can effectively solubilize 9-NC, avoid the macrophages in vitro and has a higher anti-tumor activity than both drug-loaded MPEG-DSPE micelles and free anticancer agents. The folate-conjugated polymer micelle which can avoid the macrophages is a kind of promising carrier for poorly soluble anticancer agents via folate receptor (FR) that mediated endocytosis to target tumor cells. (c) 2009 Elsevier B.V. All rights reserved.