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Download fileAn ex Vivo Model Enables Systematic Investigation of the Intestinal Absorption and Transcytosis of Oral Particulate Nanocarriers
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posted on 28.04.2021, 09:45 authored by Zhengyang Jia, Anthony Wignall, Ludivine Delon, Zhaobin Guo, Clive Prestidge, Benjamin ThierryNanoparticulate
formulations are being developed toward enhancing
the bioavailability of orally administrated biologics. However, the
processes mediating particulate carriers’ intestinal uptake
and transport remains to be fully elucidated. Herein, an optical clearing-based
whole tissue mount/imaging strategy was developed to enable high quality
microscopic imaging of intestinal specimens. It enabled the distribution
of nanoparticles within intestinal villi to be quantitatively analyzed
at a cellular level. Two-hundred and fifty nm fluorescent polystyrene
nanoparticles were modified with polyethylene glycol (PEG), Concanavalin
A (ConA), and pectin to yield mucopenetrating, enterocyte targeting,
and mucoadhesive model nanocarriers, respectively. Introducing ConA
on the PEGylated nanoparticles significantly increased their uptake
in the intestinal epithelium (∼4.16 fold for 200 nm nanoparticle
and ∼2.88 fold for 50 nm nanoparticles at 2 h). Moreover, enterocyte
targeting mediated the trans-epithelial translocation of 50 nm nanoparticles
more efficiently than that of the 200 nm nanoparticles. This new approach
provides an efficient methodology to obtain detailed insight into
the transcytotic activity of enterocytes as well as the barrier function
of the constitutive intestinal mucus. It can be applied to guide the
rational design of particulate formulations for more efficient oral
biologics delivery.
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50 nm nanoparticlesOral Particulate Nanocarriers Nanop...transcytotic activity200 nm nanoparticles2 htrans-epithelial translocationbarrier functionpolystyrene nanoparticlesPEGylated nanoparticles200 nm nanoparticleenterocyteIntestinal Absorptionbiologics deliveryadministrated biologicsVivo Model Enables Systematic Inves...polyethylene glycolmucoadhesive model nanocarriers