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Quantitative approaches to delineate paracellular diffusion in cultured epithelial cell monolayers
A Adson1, T J Raub, P S Burton
1Pharmaceutical Chemistry Department, University of Kansas, Lawrence 66045.
Journal of Pharmaceutical Sciences
|November 1, 1994
Summary
Researchers quantified the paracellular diffusion route using cultured epithelial cells. They modeled molecular size and charge effects on tight junction permeability, aiding drug delivery research.
Area of Science:
- Cell biology
- Biophysics
- Pharmacology
Background:
- Understanding transcellular diffusion is crucial for drug delivery.
- Identifying paracellular transport is key to optimizing molecule permeability across cell monolayers.
Purpose of the Study:
- To characterize the apparent diameter of junctional pores in epithelial cell monolayers.
- To quantitatively delineate factors affecting paracellular diffusion using a novel modeling approach.
Main Methods:
- Utilized various epithelial cell monolayers (Caco-2, MDCK, alveolar).
- Employed hydrophilic extracellular permeants with varying molecular radii and charges (neutral, anionic, cationic, zwitterionic).
- Applied a model for molecular size-restricted diffusion within a negative electrostatic field.
Main Results:
- The model quantitatively delineated rate-determining steps and factors of the paracellular route.
- Protonated amines showed faster pore permeation than neutral molecules; organic anions permeated slower.
- The influence of molecular charge on permeation diminished with increasing molecular size.
Conclusions:
- The study provides a quantitative method to assess paracellular transport.
- This approach can analyze changes in junctional pore size due to pharmacological interventions.
- Findings are applicable to optimizing absorption promoters and adjuvants for drug delivery.