Open AccessDetecting ordered small molecule drug aggregates in live macrophages: a multi-parameter microscope image data acquisition and analysis strategy
Author(s) -
Phillip Rzeczycki,
Gi Sang Yoon,
Rahul K. Keswani,
Sudha Sud,
Kathleen A. Stringer,
Gus R. Rosania
Publication year - 2017
Publication title -
biomedical optics express
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.362
H-Index - 86
ISSN - 2156-7085
DOI - 10.1364/boe.8.000860
Subject(s) - microscopy , drug , biophysics , small molecule , fluorescence , materials science , intracellular , fluorescence microscope , molecule , fluorescence lifetime imaging microscopy , molecular imaging , nanotechnology , chemistry , in vivo , pharmacology , pathology , biology , medicine , optics , biochemistry , physics , microbiology and biotechnology , organic chemistry
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.