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在仿生微流控系统中使用自组装明胶-油酸纳米颗粒的剪切应力依赖性靶向效率

Shear Stress-Dependent Targeting Efficiency Using Self-Assembled Gelatin-Oleic Nanoparticles in a Biomimetic Microfluidic System.

作者信息

Kang Taehee, Park Chulhun, Meghani Nileshkumar, Tran Thao T D, Tran Phuong H L, Lee Beom-Jin

机构信息

College of Pharmacy, Ajou University, Suwon 16499, Korea.

Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton AB T6G 2E1, Canada.

出版信息

Pharmaceutics. 2020 Jun 16;12(6):555. doi: 10.3390/pharmaceutics12060555.

Abstract

Cellular properties and microenvironments, as well as the characteristics of nanoparticles (NPs), affect the cellular uptake and cytotoxic effects of drug-loaded NPs. Since there is fluid flow in the human blood system, fluid flow also affects the drug delivery efficiency of NPs. This study aimed to evaluate the cellular behaviors of drug-loaded soft NPs on A549 cancer cells under different levels of shear stress (0.5, 5, and 50 dynes/cm) in the biomimetic microfluidic system. The soft self-assembled NPs were formed by the gelatin-oleic conjugate (GOC). The poorly water-soluble coumarin-6 or paclitaxel (PTX) were used as model markers for encapsulation within self-assembled NPs (C-GONs or PTX-GONs, respectively). The cellular uptake of C-GONs was found to be improved with shear-stress dependence. The inhibitory concentration (IC) of PTX-GONs at 0.5, 5, and 50 dynes/cm was 0.106 µg/mL, 0.108 µg/mL, and 0.091 µg/mL, respectively, as compared to 0.138 µg/mL in a static condition. The cell killing efficiency of PTX-GONs was increased in the highest shear stress of 50 dynes/cm in the static condition, and other levels of shear stress in dynamic conditions.

摘要

细胞特性、微环境以及纳米颗粒(NPs)的特性都会影响载药纳米颗粒的细胞摄取和细胞毒性作用。由于人体血液系统中存在流体流动,流体流动也会影响纳米颗粒的药物递送效率。本研究旨在评估在仿生微流控系统中,不同剪切应力水平(0.5、5和50达因/平方厘米)下,载药软质纳米颗粒对A549癌细胞的细胞行为。软质自组装纳米颗粒由明胶-油酸共轭物(GOC)形成。将水溶性差的香豆素-6或紫杉醇(PTX)用作模型标记物,分别封装在自组装纳米颗粒(分别为C-GONs或PTX-GONs)中。发现C-GONs的细胞摄取随剪切应力依赖性而提高。与静态条件下的0.138微克/毫升相比,PTX-GONs在0.5、5和50达因/平方厘米时的抑制浓度(IC)分别为0.106微克/毫升、0.108微克/毫升和0.091微克/毫升。在静态条件下50达因/平方厘米的最高剪切应力以及动态条件下的其他剪切应力水平下,PTX-GONs的细胞杀伤效率均有所提高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a29/7356760/bd44f837af93/pharmaceutics-12-00555-g001.jpg

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