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Surface modification of milk exosomes with hydrophilic and zwitterionic peptides improves stability in the gastrointestinal tract, permeability through intestinal mucus, and uptake into epithelial cells, thereby markedly increasing the efficiency of oral administration for gene delivery.
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Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core‐Shell Silica Nanoparticles
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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- Award ID(s):
- 1719875
- PAR ID:
- 10549101
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Publisher / Repository:
- Wiley Online Library
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 36
- Issue:
- 1
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/adma.202305937
