Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core‐Shell Silica Nanoparticles - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Advanced Materials Année : 2023

Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core‐Shell Silica Nanoparticles

Jacob Erstling
Nirmalya Bag
Thomas Gardinier
Ferdinand Kohle
Naedum Domnwachukwu
Teresa Kao
Melik Turker
Rachel Lee
Nada Naguib
Lieihn Tsaur
Dana Chapman
Saurabh Mehta
Richard Cerione
Barbara Baird
Ulrich Wiesner

Résumé

Abstract Oral delivery, while a highly desirable form of nanoparticle‐drug administration, is limited by challenges associated with overcoming several biological barriers. Here we study how fluorescent and poly(ethylene glycol)‐coated (PEGylated) core‐shell silica nanoparticles with sizes from 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies on a quasi‐total internal reflection fluorescence microscope setup, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco‐2 cell monolayers mimicking the intestinal epithelia, we observe that ultrasmall nanoparticles below 10 nm diameter (C’ dots) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage associated with tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C’ dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C’ dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health. This article is protected by copyright. All rights reserved

Domaines

Chimie Matériaux
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Dates et versions

hal-04300089 , version 1 (22-11-2023)

Identifiants

Citer

Jacob Erstling, Nirmalya Bag, Thomas Gardinier, Ferdinand Kohle, Naedum Domnwachukwu, et al.. Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core‐Shell Silica Nanoparticles. Advanced Materials, 2023, ⟨10.1002/adma.202305937⟩. ⟨hal-04300089⟩
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