基于叶酸受体介导的载吉西他滨壳聚糖纳米粒的胰腺癌靶向递药系统

基于叶酸受体介导的载吉西他滨壳聚糖纳米粒的胰腺癌靶向递药系统

基于叶酸受体介导的载吉西他滨壳聚糖纳米粒的胰腺癌靶向递药系统 徐师，许茜*

东南大学，地址南京市丁家桥87号公共卫生学院，210009

*Email: q_xu68@http://www.77cn.com.cn

摘要：本文采用同轴静电喷射制备叶酸-壳聚糖-吉西他滨核壳纳米粒子（FA-Chi-Gem纳米粒子）以达到靶向治疗胰腺癌的目的，以叶酸-壳聚糖溶液为外层包封溶液，吉西他滨为被包封的药物。同时考察了纳米粒形成过程中不同溶液性质和操作参数的影响，结果表明，叶酸-壳聚糖浓度、乙酸和三氟乙醇的浓度、外加电压以及流速是影响静电喷射的重要参数。在最优化的条件下，所制得的核壳纳米粒平均粒径大约为300nm。载药量和包封率分别为3.91±0.12%和85.37±4.9%。药物的释放曲线在pH 7.4和pH 5.0环境下均显示出了5 h快速释放过程，之后约72 h内持续释放，且在pH 5.0环境下释药更快。体外细胞实验结果表明所制得的纳米粒对胰腺肿瘤细胞（BXPC3）具有靶向作用，且细胞毒性显著提高，体现出FA-Chi-Gem纳米粒子在靶向基础上对胰腺肿瘤细胞抑制效果的增强。

关键词：叶酸；壳聚糖；吉西他滨；同轴静电喷射；胰腺肿瘤靶向递药系统

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Pancreatic Tumor-targeted Drug Delivery System Based on

Folate-Chitosan-Gemcitabine Nanoparticles *

School of Public Health, Southeast University, Ding Jiaqiao 87#, Nanjing, 210009

Abstract: Core-shell nanoparticles were prepared by coaxial electrospray technology, with folate-chitosan as the polymeric coating material and gemcitabine as the encapsulated drug. By optimizing the electrospray parameters, the average diameter of the nanoparticles was about 300nm with drug loading and encapsulation efficiency of

3.91% and 85.4%. The drug release kinetics revealed a controlled initial burst release followed by a sustained release over a period of 72 h at pH 7.4 and pH 5.0, and at pH 5.0 the drug released more quickly. Moreover, cellular uptake experiment confirmed that the folate conjugated core-shell nanoparticles had high pancreatic cancer (BXPC3) cells uptake efficiency. And the in vitro cell cytotoxicity test displayed that they had remarkable cytotoxicity towards BXPC3 cells. This study indicates that coaxial electrospray is a facile technique in producing core-shell nanoparticles encapsulating hydrophilic small molecule drugs, and the folate conjugated core-shell nanoparticles is very much effective as pancreatic tumor-targeted delivery system.

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