title: Detecting ordered small molecule drug aggregates in live macrophages: a multi-parameter microscope image data acquisition and analysis strategy.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Rzeczycki
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
authors.forename: Gi Sang
authors.initials: GS
authors.lastname: Yoon
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
authors.forename: Rahul K
authors.initials: RK
authors.lastname: Keswani
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Sud
authors.affiliation: Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Stringer
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
authors.forename: Gus R
authors.initials: GR
authors.lastname: Rosania
keywords: (170.0110) Imaging systems; (170.1530) Cell analysis; (170.3880) Medical and biological imaging; (260.5430) Polarization