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

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

Journal Article · 22 November 2023 · Advanced Materials

DOI: https://doi.org/10.1002/adma.202305937 · OSTI ID:2221892

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^[1]; Tallman, James F. ^[3]; Malarkey, Henry F. ^[7];

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Department of Materials Science and Engineering Cornell University Ithaca NY 14853 USA, Department of Biomedical Engineering Cornell University Ithaca NY 14853 USA
Department of Chemistry and Chemical Biology Cornell University Ithaca NY 14853 USA
Department of Materials Science and Engineering Cornell University Ithaca NY 14853 USA
Department of Materials Science and Engineering Cornell University Ithaca NY 14853 USA, Department of Chemistry and Chemical Biology Cornell University Ithaca NY 14853 USA
Department of Biomedical Engineering Cornell University Ithaca NY 14853 USA
Department of Biomedical Sciences Cornell University Ithaca NY 14853 USA
Department of Applied and Engineering Physics Cornell University Ithaca NY 14853 USA
Center for Precision Nutrition and Health Division of Nutritional Sciences Cornell University Ithaca NY 14853 USA
Department of Materials Science and Engineering Cornell University Ithaca NY 14853 USA, Kavli Institute at Cornell for Nanoscale Science Cornell University Ithaca NY 14853 USA

Abstract Oral delivery, while a highly desirable form of nanoparticle‐drug administration, is limited by challenges associated with overcoming several biological barriers. Here, 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.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0010560

OSTI ID:: 2221892

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

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: Germany

Language:: English

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