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

Pharmaceutics

Chadi Abbara¹  Marie Briet¹  Samuel Legeay²  Norraseth Kaeokhamloed²  Emillie Roger²  Jérôme Béjaud²  Nolwenn Lautram²  Rodolphe Perrot³  Florence Manero³ 

[1] Laboratoire de Pharmacologie-Toxicologie, CRPV, Angers University Hospital Center, F-49000 Angers, France;MINT, INSERM U1066, CNRS UMR 6021, SFR ICAT, University of Angers, F-49000 Angers, France;SCIAM, SFR ICAT, University of Angers, F-49000 Angers, France;

关键词: intestinal absorption;    Caco-2;    HMEC-1;    apparent permeability;    lipid nanocapsule;    förster resonance energy transfer;   

DOI  :  10.3390/pharmaceutics13050595

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown