Xu Juan, Liu Chong, Xu Yi-ning, Shan Wei, Liu Min, Huang Yuan
Yao Xue Xue Bao. 2015 Jul;50(7):893-8.
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.
本研究考察了一种由改性三甲基壳聚糖（TMC）构建的纳米药物递送系统。TMC 经整合素受体 avβ3 的配体 cRGDyk 改性。采用单因素筛选法优化处方，其中 TMC 纳米颗粒（TMC NPs）和 cRGDyk 改性 TMC 纳米颗粒（C-TMC NPs）的粒径分别为（240.3±4.2）nm 和（259.5±3.3）nm。这两种纳米颗粒的电势分别为（33.5±0.8）mV 和（25.7±1.6）mV。包封率分别为（76.0±2.2）%和（74.4±2.0）%。载药效率分别为（50.1±2.1）%和（26.1±1.0）%。然后，使用 Caco-2 细胞系研究了 TMC NPs 和 C-TMC NPs 的细胞摄取、摄取机制和转运效率。C-TMC NPs 的摄取率和累积药物转运剂量分别比 TMC NPs 高 1.98 倍和 2.84 倍。机制研究表明，小窝介导的内吞作用、网格蛋白介导的内吞作用和巨胞饮作用均参与了 TMC NPs 和 C-TMC NPs 的细胞间摄取。此外，游离的 cRGDyk 可显著抑制 C-TMC NPs 的摄取。
