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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Europium complexes as novel indicators of paracellular diffusion
Zhihan Xu1, Chengyue Zhang, Yue Zhang
1State Key Laboratories of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, PR China.
Chemistry & Biodiversity
|September 15, 2012
Summary
New Europium (Eu) complexes serve as effective, non-toxic indicators for measuring paracellular permeation across cell layers. These probes accurately assess tight junction integrity, crucial for drug absorption and toxicity studies.
Area of Science:
- Biomedical Engineering
- Materials Science
- Pharmacology
Background:
- Assessing paracellular permeation is vital for understanding drug toxicity, particularly with metal-based drugs.
- Validating cell monolayer integrity is essential for drug absorption models.
- Development of novel paracellular diffusion indicators is an active research area.
Purpose of the Study:
- To synthesize and evaluate three novel Europium (Eu) complexes as potential paracellular indicators.
- To investigate the permeation properties and toxicity of these Eu complexes on Madin-Darby canine kidney (MDCK) cells.
- To determine the correlation between Eu complex permeation and tight junction integrity.
Main Methods:
- Preparation of three Europium complexes: [Eu(dtpa)], [Eu(dtpa)(BSA)], and [Eu(dtpa)(PLL)].
- Testing permeation properties and cytotoxicity on Madin-Darby canine kidney (MDCK) cells.
- Measurement of apparent permeability (P(app)) and trans-epithelial electric resistance (TEER).
- Time-resolved fluorescence assays conducted in a high-sensitivity, background-free mode.
Main Results:
- All three Eu complexes demonstrated no toxicity to MDCK cells.
- The probes exclusively permeated across the MDCK cell monolayer via paracellular pathways.
- Eu complex permeation showed a high correlation with decreased trans-epithelial electric resistance (TEER), indicating response to tight junction changes.
- Time-resolved fluorescence assays confirmed the probes' utility.
Conclusions:
- The synthesized Europium complexes are effective and practical indicators for paracellular permeation.
- These novel probes can reliably assess tight junction integrity and monolayer permeability.
- Eu complexes offer a valuable tool for drug toxicity and absorption studies.
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