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Detecting ordered small molecule drug aggregates in live macrophages: a multi-parameter microscope image data
Phillip Rzeczycki1, Gi Sang Yoon1, Rahul K Keswani1
1Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
Biomedical Optics Express
|March 9, 2017
Summary
Researchers developed a new imaging platform to detect crystal-like drug inclusions (CLDIs) formed by poorly soluble drugs within cells. This method aids in studying drug sequestration and molecular aggregation in vivo.
Area of Science:
- Biomedical Imaging
- Pharmacology
- Cell Biology
Background:
- Poorly soluble small molecule drugs can precipitate intracellularly as crystal-like drug inclusions (CLDIs) after prolonged oral administration.
- These CLDIs can impact drug efficacy and cellular function, necessitating methods for their detection and study.
Purpose of the Study:
- To develop and validate a quantitative multi-parameter imaging platform for detecting and characterizing intracellular CLDIs.
- To assess the formation of ordered molecular aggregates of poorly soluble drugs within cells.
Main Methods:
- Utilized a quantitative multi-parameter imaging platform measuring fluorescence and polarization diattenuation signals.
- Employed clofazimine (CFZ), an FDA-approved drug, as a model compound for system validation.
- Analyzed microscopy images of cells containing intracellular CLDIs.
Main Results:
- The imaging platform successfully measured fluorescence and polarization diattenuation signals from cells with CLDIs.
- Demonstrated the capability to study drug-sequestering macrophages using the developed platform.
- Confirmed the detection of ordered molecular aggregates formed by poorly soluble drugs in vivo.
Conclusions:
- A quantitative multi-parameter microscopy image analysis platform provides a novel method for studying intracellular CLDIs.
- This platform enables the investigation of drug sequestration and the formation of ordered molecular aggregates in biological systems.
- The system is valuable for understanding the behavior of poorly soluble drugs within living organisms.
