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

发布时间：2019-01-16 01:08

【摘要】：本文拟构建整合素配体c RGDyk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)m V;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c RGDyk可显著抑制C-TMC NPs的细胞摄取。
[Abstract]:In order to improve the oral bioavailability of insulin, a trimethyl chitosan nano-delivery system modified with c RGDyk integrin ligands was constructed in this paper. The single factor screening method was used to optimize the formulation of (TMC NPs) and ligand modified nanoparticles (C-TMC NPs), = (240.3 卤4. 2) and (259.5 卤3. 3) nm;, respectively). The potential was (33.5 卤0.8) and (25.7 卤1.6) m V; entrapment efficiency was (76.0 卤2.2)% and (74.4 卤2.0)%, the drug loading was (50.1 卤2.1)% and (26.1 卤1.0)%, respectively. The cellular uptake, transmembrane and related transport mechanisms of TMC NPs and C-TMC NPs were investigated using Caco-2 cells as a model. The uptake of C-TMC NPs and the cumulative drug transmittance of C-TMC NPs were 1.98 and 2.84 times higher than those of TMC NPs, respectively. It was found that the cellular uptake of both, TMC NPs and C-TMC NPs was mediated by grid protein, fossa protein mediated active transport and large cell drink, and free c RGDyk could significantly inhibit the cellular uptake of C-TMC NPs.
【作者单位】：四川大学华西药学院;
【基金】：国家自然科学基金资助项目(81173010)
【分类号】：R96

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