Evaluation of drug carrier hepatotoxicity using primary cell culture models
Evaluation of drug carrier hepatotoxicity using primary cell culture models
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DOI：
10.1016/j.nano.2023.102651
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发表时间：
2023-01-17
影响因子：
5.4
通讯作者：
Usta，O. Berk
中科院分区：
文献类型：
--
作者：
Kibar，Gunes;Dutta，Subhadeep;Usta，O. Berk
本研究旨在建立大鼠肝细胞原代培养模型，以评价药物载体(脂聚合物纳米粒)的时间剂量依赖性肝毒性效应。用原代培养的大鼠肝细胞测定药物载体文库的半数抑制浓度(IC50)。用白蛋白和尿素分泌物测定，药物载体文库在浓度为50μg/mL时对原代大鼠肝细胞是良性的。白蛋白作为一种肝脏生物标志物，与尿素相比，在测定LPN的IC50值方面表现出更敏感和更快的结果。肝脏生物标志物的时间测量，包括尿素和白蛋白，以及严格的物理化学(流体直径、表面电荷等)。在筛选中评价药物载体文库的肝毒性时，应结合特性。
This study aims to establish a primary rat hepatocyte culture model to evaluate dose-dependent hepatotoxic effects of drug carriers (lipopolymer nanoparticles; LPNs) temporal. Primary rat hepatocyte cell cultures were used to determine half-maximal Inhibition Concentrations (IC50) of the drug-carrier library. Drug-carrier library, at concentrations <50 μg/mL, is benign to primary rat hepatocytes as determined using albumin and urea secretions. Albumin, as a hepatic biomarker, exhibited a more sensitive and faster outcome, compared to urea, for the determination of the IC50value of LPNs. Temporal measurements of hepatic biomarkers including urea and albumin, and rigorous physicochemical (hydrodynamic diameter, surface charge, etc.) characterization, should be combined to evaluate the hepatotoxicity of drug carrier libraries in screens.