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Biomimetic Artificial Membrane Permeability Assay over Franz Cell Apparatus Using BCS Model Drugs.

Leonardo de Souza Teixeira1, Tatiana Vila Chagas2, Antonio Alonso3

  • 1Institute of Pharmaceutical Sciences, Goiânia, Goiás 74175-100, Brazil.

Pharmaceutics
|October 22, 2020
PubMed
Summary

A new biomimetic artificial membrane permeability assay (Franz-PAMPA) was validated for drug discovery. This method accurately predicts oral drug absorption by mimicking the intestinal lipid barrier, aiding in early-stage pharmaceutical research.

Keywords:
BCS drugsFranz cellFranz–PAMPAbiomimetic membranepassive drug transport

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Area of Science:

  • Pharmacology
  • Biophysical Chemistry
  • Drug Discovery

Background:

  • Oral drug absorption is significantly influenced by intestinal epithelial cell permeability.
  • Accurate prediction of drug permeability is crucial for efficient drug discovery and development.
  • Existing permeability assays may not fully replicate the complex biological environment of the intestine.

Purpose of the Study:

  • To validate a biomimetic artificial membrane permeability assay (Franz-PAMPA) using a Franz cell apparatus.
  • To assess the biomimetic properties and performance of Franz-PAMPA in predicting oral drug absorption.
  • To compare Franz-PAMPA performance with established methods like Caco-2 cell permeability.

Main Methods:

  • Validation of the Franz-PAMPA assay using high (metoprolol) and low (mannitol) permeability drugs.
  • Characterization of biomimetic properties using electron paramagnetic resonance spectroscopy (EPR).
  • Measurement of apparent permeability (Papp) for 14 model drugs and correlation with human fraction absorbed (Fa%).

Main Results:

  • Franz-PAMPA demonstrated lipidic barrier resistivity, with lower Papp values for mannitol and metoprolol compared to non-impregnated membranes.
  • The assay showed an acceptable log-linear correlation (R² = 0.664) between Papp and human Fa%.
  • Franz-PAMPA performance was comparable to Caco-2 cell permeability assays (R² = 0.805).

Conclusions:

  • The Franz-PAMPA assay, utilizing a Franz cell apparatus, is validated as a reliable tool for drug discovery.
  • This biomimetic assay effectively models intestinal drug permeability, aiding in the prediction of oral absorption.
  • Franz-PAMPA offers a valuable method for early-stage drug development, improving the efficiency of candidate selection.