高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (10): 2239-2245.doi: 10.7503/cjcu20140504

• 高分子化学 • 上一篇    下一篇

载紫杉醇星型M-PLA-TPGS纳米颗粒的合成及其用于前列腺癌治疗药物载体的研究

王海1, 张超1, 张琳华1, 刘兰霞1, 郑义2, 朱敦皖1()   

  1. 1. 中国医学科学院, 北京协和医学院, 生物医学工程研究所,天津市生物医学材料重点实验室, 天津 300192
    2. 清华大学深圳研究生院, 深圳 518055
  • 收稿日期:2014-06-03 出版日期:2014-10-10 发布日期:2014-09-18
  • 作者简介:联系人简介: 朱敦皖, 男, 博士, 副研究员, 主要从事生物医学材料研究. E-mail: zhudunwan@163.com
  • 基金资助:
    国家自然科学基金(批准号: 81100100, 51103180, 31200674)资助

Synthesis of Nanoparticles of Star-shaped Mannitol-core PLA-TPGS Copolymer for Delivery of Paclitaxel and Activity of Anti-prostate Cancer

WANG Hai1, ZHANG Chao1, ZHANG Linhua1, LIU Lanxia1, ZHENG Yi2, ZHU Dunwan1,*()   

  1. 1. Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, China
    2. Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China
  • Received:2014-06-03 Online:2014-10-10 Published:2014-09-18
  • Contact: ZHU Dunwan E-mail:zhudunwan@163.com
  • Supported by:
    Supported by the National Natural Science Foundation of China(Nos.81100100, 51103180, 31200674)

摘要:

合成了一种甘露醇引发的星型共聚物甘露醇-聚乳酸-聚乙三醇1000维生素E琥珀酸酯(M-PLA-TPGS). 利用纳米沉淀法制备载紫杉醇M-PLA-TPGS纳米颗粒. 纳米颗粒近似球形, 粒径分布较窄. 对载药纳米颗粒进行粒径、 表面电荷、 载药量、 包封率和体外药物释放的表征, 结果表明, 体外药物释放呈双相释放模型, M-PLA-TPGS纳米颗粒在前列腺癌PC-3细胞中的摄取水平要高于PLGA和PLA-TPGS纳米颗粒. 载紫杉醇M-PLA-TPGS纳米颗粒对于前列腺癌细胞的的毒性显著高于载紫杉醇PLA-TPGS纳米颗粒和商业制剂Taxol, 证明星型M-PLA-TPGS聚合物作为纳米药物载体优于线性PLGA和PLA-TPGS聚合物.

关键词: 星型共聚物, 紫杉醇, 聚乳酸, 聚(乳酸-羟基乙酸)共聚物, 纳米颗粒, 药物递送, 癌症纳米技术, 前列腺癌, 细胞毒性

Abstract:

The objective of this research is to fabricate novel nanoparticles(NPs) of star-shaped mannitol-functionalized polylactic acid-D-α-tocopheryl polyethylene glycol 1000 suclinat(PLA-TPGS) copolymer for paclitaxel delivery for prostate cancer treatment, and evaluate their therapeutic effects in prostate cancer cell line in comparison with the linear PLGA NPs and PLA-TPGS NPs. The paclitaxel-loaded M-PLA-TPGS NPs, prepared by a modified nano-precipitation method, were observed by field emission scanning electron microscopy(FESEM) to be near-spherical shape with narrow size distribution. The drug-loaded NPs were further characterized in terms of size, surface charge, drug content, encapsulation efficiency and in vitro drug release. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release. The cellular uptake level of M-PLA-TPGS NPs was demonstrated higher than linear PLGA NPs and PLA-TPGS NPs in PC-3 cells. The data also showed that the paclitaxel-loaded M-PLA-TPGS nanoparticles have higher antitumor efficacy than that of linear PLA-TPGS nanoparticles and commercial Taxol in vitro. The star-shaped copolymer M-PLA-TPGS could be used as a potential and promising molecular biomaterial applied in developing novel nanoformulation for prostate cancer treatment.

Key words: Star-shaped copolymer, Paclitaxel, Polylactic acid, Poly(lactic-co-glycolic acid), Nano-particles, Drug delivery, Cancer nanotechnology, Prostate cancer, Cytotoxicity

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