Rzeczycki Phillip, Yoon Gi Sang, Keswani Rahul K, Sud Sudha, Stringer Kathleen A, Rosania Gus R
Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
Biomed Opt Express. 2017 Jan 13;8(2):860-872. doi: 10.1364/BOE.8.000860. eCollection 2017 Feb 1.
Following prolonged administration, certain orally bioavailable but poorly soluble small molecule drugs are prone to precipitate out and form crystal-like drug inclusions (CLDIs) within the cells of living organisms. In this research, we present a quantitative multi-parameter imaging platform for measuring the fluorescence and polarization diattenuation signals of cells harboring intracellular CLDIs. To validate the imaging system, the FDA-approved drug clofazimine (CFZ) was used as a model compound. Our results demonstrated that a quantitative multi-parameter microscopy image analysis platform can be used to study drug sequestering macrophages, and to detect the formation of ordered molecular aggregates formed by poorly soluble small molecule drugs in animals.
长期给药后，某些口服生物利用度高但溶解性差的小分子药物容易沉淀出来，并在活生物体细胞内形成晶体状药物包涵体（CLDIs）。在本研究中，我们提出了一个定量多参数成像平台，用于测量含有细胞内CLDIs的细胞的荧光和偏振衰减信号。为了验证该成像系统，使用了美国食品药品监督管理局（FDA）批准的药物氯法齐明（CFZ）作为模型化合物。我们的结果表明，定量多参数显微镜图像分析平台可用于研究药物隔离巨噬细胞，并检测动物体内难溶性小分子药物形成的有序分子聚集体。
