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

Erstling, Jacob A.; Bag, Nirmalya; Gardinier, Thomas C.; Kohle, Ferdinand F. E.; DomNwachukwu, Naedum; Butler, Scott D.; Kao, Teresa; Ma, Kai; Turker, Melik Z.; Feuer, Grant B.; Lee, Rachel; Naguib, Nada; Tallman, James F.; Malarkey, Henry F.; Tsaur, Lieihn; Moore, William L.; Chapman, Dana V.; Aubert, Tangi; Mehta, Saurabh; Cerione, Richard A.; Weiss, Robert S.; Baird, Barbara A.; Wiesner, Ulrich B.

doi:10.1002/adma.202305937

Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core‐Shell Silica Nanoparticles (in EN)

Journal Article · Sat Sep 09 04:00:00 EDT 2023 · Advanced Materials

DOI:https://doi.org/10.1002/adma.202305937· OSTI ID:2575758

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Cornell Univ., Ithaca, NY (United States)

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, in this study, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, 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, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C’ dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through 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.

View Accepted Manuscript (DOE)

Research Organization:: Cornell Univ., Ithaca, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); National Science Foundation (NSF)

Grant/Contract Number:: SC0010560

OSTI ID:: 2575758

Alternate ID(s):: OSTI ID: 2221892

Journal Information:: Advanced Materials, Journal Name: Advanced Materials Journal Issue: 1 Vol. 36; ISSN 1521-4095; ISSN 0935-9648

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: EN

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