药学学报, 2015, 50(7): 893-898
引用本文:
许娟, 刘冲, 许艺苧, 山伟, 刘敏, 黄园. 整合素受体靶向的载胰岛素三甲基壳聚糖纳米给药系统细胞摄取及转运机制[J]. 药学学报, 2015, 50(7): 893-898.
XU Juan, LIU Chong, XU Yi-ning, SHAN Wei, LIU Min, HUANG Yuan. Mechanism of cellular uptake and transport mediated by integrin receptor targeting trimethyl chitosan nanoparticles[J]. Acta Pharmaceutica Sinica, 2015, 50(7): 893-898.

整合素受体靶向的载胰岛素三甲基壳聚糖纳米给药系统细胞摄取及转运机制
许娟, 刘冲, 许艺苧, 山伟, 刘敏, 黄园
四川大学华西药学院, 四川 成都 610041
摘要:
本文拟构建整合素配体cRGDyk修饰的三甲基壳聚糖纳米给药系统, 以期提高胰岛素的口服生物利用度。采用单因素筛选法对其处方进行优化, 筛选最优处方制得非配体修饰纳米粒 (TMC NPs) 和配体修饰纳米粒 (C-TMC NPs), 粒径分别为 (240.3 ± 4.2) 和 (259.5 ± 3.3) nm; 电位分别为 (33.5 ± 0.8) 和 (25.7 ± 1.6) mV; 包封率分别为 (76.0 ± 2.2) % 和 (74.4 ± 2.0) %; 载药量分别为 (50.1 ± 2.1) % 和 (26.1 ± 1.0) %。以Caco-2细胞为模型, 考察了TMC NPs和C-TMC NPs的细胞摄取、跨膜及相关转运机制。C-TMC NPs的摄取及药物累计透过量较TMC NPs分别提高了1.98倍和2.84倍。研究发现, TMC NPs和C-TMC NPs的细胞摄取均由网格蛋白、小窝蛋白介导的主动转运及大胞饮参与, 且游离的cRGDyk可显著抑制C-TMC NPs的细胞摄取。
关键词:    αvβ3整合素受体      cRGDyk多肽      三甲基壳聚糖纳米粒     
Mechanism of cellular uptake and transport mediated by integrin receptor targeting trimethyl chitosan nanoparticles
XU Juan, LIU Chong, XU Yi-ning, SHAN Wei, LIU Min, HUANG Yuan
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Abstract:
This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.
Key words:    alpha-v beta-3 integrin receptor    cRGDyk peptide    N-trimethyl chitosan nanoparticle   
收稿日期: 2015-03-05
基金项目: 国家自然科学基金资助项目 (81173010).
通讯作者: 黄园
Email: huangyuan0@163.com
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