Pharmaceutics (Apr 2021)

New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules

  • Norraseth Kaeokhamloed,
  • Emillie Roger,
  • Jérôme Béjaud,
  • Nolwenn Lautram,
  • Florence Manero,
  • Rodolphe Perrot,
  • Marie Briet,
  • Chadi Abbara,
  • Samuel Legeay

DOI
https://doi.org/10.3390/pharmaceutics13050595
Journal volume & issue
Vol. 13, no. 5
p. 595

Abstract

Read online

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on a Transwell® insert has been developed. The model has been validated for (a) membrane morphology by transmission electron microscope (TEM); (b) ZO-1 and β-catenin expression by immunoassay; (c) membrane integrity by trans-epithelial electrical resistance (TEER) measurement; and (d) apparent permeability of drugs from different biopharmaceutical classification system (BCS) classes. Lipid nanocapsules (LNCs) were formulated with different sizes (55 and 85 nm) and surface modifications (DSPE-mPEG (2000) and stearylamine). Nanocapsule integrity and particle concentration were monitored using the Förster resonance energy transfer (FRET) technique. The result showed that surface modification by DSPE-mPEG (2000) increased the absorption of 55-nm LNCs in the coculture model but not in the Caco-2. Summarily, the coculture model was validated as a tool for evaluating the intestinal absorption of drugs and nanoparticles. The new coculture model has a different LNCs absorption mechanism suggesting the importance of intestinal endothelium and reveals that the surface modification of LNCs can modify the in vitro oral absorption.

Keywords