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

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

doi:10.3390/pharmaceutics13050595

Norraseth Kaeokhamloed, Rodolphe Perrot + Show 7 more

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https://doi.org/10.3390/pharmaceutics13050595

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Abstract

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.

Highlights

IntroductionSome drugs present a low oral bioavailability due to low drug solubility or low intestinal permeability
The cell morby Bannunah et al [54], who described that anionic polystyrene nanoparticles (PS-NPs) had phology, membrane integrity, and drug permeability were validated and proved that the much higher transportation across the Caco-2 model than cationic PS-NPs
Transcytosis of anionic PS-NPs mainly occurred via the caveolae-mediated pathway, while it Improving the conventional Caco-2 model by adding the endothelium layer could change was not the case for cationic PS-NPs whose transcytosis occurred via the clathrin-mediated the absorption pattern of lipid nanocapsules (LNCs) but not drugs in solution

Summary

Introduction

Some drugs present a low oral bioavailability due to low drug solubility or low intestinal permeability. This low permeability can be explained by the intestine’s complex multilayer structure, consisting of the mucus barrier, the enterocytic barrier, and the endothelial barrier [1,2,3]. To improve oral drug delivery, drug encapsulation into nanocarriers, such as lipid nanocapsules (LNCs), is currently one of the most promising technologies. LNCs consist of an oily core enclosed by a shell of pegylated surfactant and phosphatidylcholine and can be prepared by a well-known lowenergy emulsification process: The phase-inversion temperature method [4,5]. LNCs have sizes ranging from 20 to 100 nm and can be prepared with different surface-chemistry

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