Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, New York, 14203, USA.
Institute for Lasers, Photonics and Biophotonics, University at Buffalo, Buffalo, New York, 14260, USA.
Pharm Res. 2019 Feb 1;36(3):44. doi: 10.1007/s11095-019-2576-9.
An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure.
A dynamic PK cell culture system was developed to more closely reflect physiologic nanoparticle/drug concentrations that are changing with time. Macrophages were cultured in standard static and PK cell culture systems with rifampin (RIF; 5 μg/ml) or β-glucan, chitosan coated, poly(lactic-co-glycolic) acid (GLU-CS-PLGA) nanoparticles (RIF equivalent 5 μg/ml) for 6 h. Intracellular RIF concentrations were measured by UPLC/MS. Antimicrobial activity against M. smegmatis was tested in both PK and static systems.
The dynamic PK cell culture system mimics a one-compartment elimination pharmacokinetic profile to properly mimic in vivo extracellular exposure. GLU-CS-PLGA nanoparticles increased intracellular RIF concentration by 37% compared to free drug in the dynamic cell culture system. GLU-CS-PLGA nanoparticles decreased M. smegmatis colony forming units compared to free drug in the dynamic cell culture system.
The PK cell culture system developed herein enables more precise simulation of human PK exposure (i.e., drug dosing and drug elimination curves) based on previously obtained PK parameters.
开发一种体外动态药代动力学（PK）细胞培养系统，以更精确地模拟生理纳米颗粒/药物暴露。
开发了一种动态 PK 细胞培养系统，以更紧密地反映随时间变化的生理纳米颗粒/药物浓度。用利福平（RIF；5μg/ml）或β-葡聚糖、壳聚糖包被的聚（乳酸-共-羟基乙酸）（GLU-CS-PLGA）纳米颗粒（RIF 等效 5μg/ml）在标准静态和 PK 细胞培养系统中培养巨噬细胞 6 小时。通过 UPLC/MS 测量细胞内 RIF 浓度。在 PK 和静态系统中测试了对耻垢分枝杆菌的抗菌活性。
动态 PK 细胞培养系统模拟了单室消除药代动力学曲线，以正确模拟体内细胞外暴露。与游离药物相比，GLU-CS-PLGA 纳米颗粒在动态细胞培养系统中使细胞内 RIF 浓度增加了 37%。与游离药物相比，GLU-CS-PLGA 纳米颗粒在动态细胞培养系统中降低了耻垢分枝杆菌的菌落形成单位。
本文开发的 PK 细胞培养系统能够根据先前获得的 PK 参数更精确地模拟人体 PK 暴露（即药物剂量和药物消除曲线）。
