赵燕敏 夏爱晓 魏颖慧 阮叶萍 李范珠. 聚山梨酯80修饰的神经毒素纳米粒跨血脑屏障转运及细胞毒性J. 药学学报, 2010,45(10): 1312-1316.
引用本文: 赵燕敏 夏爱晓 魏颖慧 阮叶萍 李范珠. 聚山梨酯80修饰的神经毒素纳米粒跨血脑屏障转运及细胞毒性J. 药学学报, 2010,45(10): 1312-1316.
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DIAO Yan-Min, Jia-Ai-Xiao, Wei-Ying-Hui, Ruan-Xie-Ping, Li-Fan-Zhu. Polysorbate-80 modified neurotoxin nanoparticle with its transport and cytotoxicity against blood-brain barrierJ. 药学学报, 2010,45(10): 1312-1316.
Citation: DIAO Yan-Min, Jia-Ai-Xiao, Wei-Ying-Hui, Ruan-Xie-Ping, Li-Fan-Zhu. Polysorbate-80 modified neurotoxin nanoparticle with its transport and cytotoxicity against blood-brain barrierJ. 药学学报, 2010,45(10): 1312-1316.
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聚山梨酯80修饰的神经毒素纳米粒跨血脑屏障转运及细胞毒性

Polysorbate-80 modified neurotoxin nanoparticle with its transport and cytotoxicity against blood-brain barrier

    摘要
  • 摘要:

    研究聚山梨酯80修饰的神经毒素纳米粒 (polysorbate-80 modified neurotoxin nanoparticle, P-80-NT-NP) 在血脑屏障 (blood-brain barrier, BBB) 体外模型上的通透性及细胞毒性。采用SD大鼠大脑分离培养脑微血管内皮细胞 (rat brain microvascular endothelial cells, rBMECs) 建立BBB体外模型, 以神经毒素 (neurotoxin, NT) 组、空白纳米粒 (nanoparticle, NP) 组和未修饰的神经毒素纳米粒 (neurotoxin nanoparticle, NT-NP) 组作为对照, MTT法考察P-80-NT-NP对rBMECs的细胞毒性; 采用Millicell insert培养rBMECs, 荧光分光光度法测定P-80-NT-NP在基底侧中NT浓度, 计算其表观通透系数。结果显示, 当NT质量浓度≤200 ng·mL-1时, NT组、NP组、NT-NP组和P-80-NT-NP组均无细胞毒性; NT质量浓度>200 ng·mL-1时, NP组、NT-NP组和P-80-NT-NP组的细胞毒性显著大于NT组 (P < 0.01), 且P-80-NT-NP组的细胞毒性较NP组和NT-NP组稍大, 但无显著性差异 (P > 0.05)。当NT质量浓度为150 ng·mL-1时, NT-NP组和P-80-NT-NP组的转运量均显著大于NT组 (P < 0.01), 且P-80-NT-NP组的转运量较NT-NP组亦有显著增加 (P < 0.05), 表明P-80修饰的NT纳米粒能跨BBB转运; 但当P-80-NT-NP质量浓度>200 ng·mL-1时, 对rBMECs产生细胞毒性, 为脑靶向纳米粒跨BBB转运的机制研究奠定基础。

     

    Abstract:

    This study was aimed at the transport across blood-brain barrier (BBB) of polysorbate-80 modified neurotoxin loaded polybutylcyanoacrylate nanoparticle (P-80-NT-NP) and its cytotoxicity.  An in vitro model of BBB using rat brain microvascular endothelial cells (rBMECs) was established.  The cytotoxicity of P-80-NT-NP was measured by the MTT assays, where neurotoxin (NT), nanoparticle (NP), neurotoxin nanoparticle (NT-NP) as control, and the permeability of P-80-NT-NP was determined by using of Millicell insert coculture with rBMECs and fluorescence spectrophotometry.  MTT results showed that NT, NP, NT-NP and P-80-NT-NP were avirulent to rBMECs when the concentration of NT was lower than 200 ng·mL-1.  But the cytotoxicity of NP, NT-NP and P-80-NT-NP would be augmented accordingly as concentration increased (P < 0.01), causing obvious reductions of cell survival rate, with no signi?cant difference between them (P > 0.05).  When the concentration of NT was 150 ng·mL-1, the permeability on rBMECs of P-80-NT-NP and NT-NP were both signi?cantly higher than that of NT (P < 0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P < 0.05).  In conclusion, polysorbate-80 modified neurotoxin nanoparticles can transport across the BBB, while concentration of NT is greater than 200 ng·mL-1, P-80-NT-NP has a little cytotoxicity against rBMECs.

     

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