ArticleInternational journal of pharmaceutics2021
The enhanced intestinal permeability of infant mice enables oral protein and macromolecular absorption without delivery technology.
Article in International journal of pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Culture Optimization of the IPEC-J2 Piglet Jejunum Cell Line for Applications in Infant Nutrition Research.Molecular nutrition & food research · 2026Article
- Maternal expression and breast milk transfer of an mRNA- encoded monoclonal antibody in a murine model of cholera.PLoS neglected tropical diseases · 2026Article
- Alternatives to animal models in gastroenterology and hepatology research.Frontiers in pharmacology · 2026Review
- Neonatal exposure to morphine results in prolonged pain hypersensitivity during adolescence, driven by gut microbial dysbiosis and gut-brain axis-mediated inflammation.Brain, behavior, and immunity · 2025Article
- Maternal milk cell components are uptaken by infant liver macrophages via extracellular vesicle mediated transport.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Using sodium glycodeoxycholate to develop a temporary infant-like gut barrier model,Frontiers in nutrition · 2025Article
- Studies on the changes in rectal permeability and intestinal microbiota with developmental age in young rats.Frontiers in microbiology · 2025Article
- Microbiota and B-1 B cell repertoire development in mice.Current opinion in immunology · 2024Review
- Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota-gut-brain axis.Nature reviews. Gastroenterology & hepatology · 2024Review
- Recent Progress in the Oral Delivery of Therapeutic Peptides and Proteins: Overview of Pharmaceutical Strategies to Overcome Absorption Hurdles.Advanced pharmaceutical bulletin · 2024Review
- Secreted IgM modulates IL-10 expression in B cells.Nature communications · 2024Article
- Microbiota-Derived Extracellular Vesicles Promote Immunity and Intestinal Maturation in Suckling Rats.Nutrients · 2023Article
- Encapsulation of Iron-Saturated Lactoferrin for Proteolysis Protection with Preserving Iron Coordination and Sustained Release.Nanomaterials (Basel, Switzerland) · 2023Article
- Enhancement of prostaglandin DFrontiers in immunology · 2023Article
- Profiling of mature-stage human breast milk cells identifies six unique lactocyte subpopulations.Science advances · 2022Article
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- Oral delivery of peptide therapeutics in infants: Challenges and opportunities.Advanced drug delivery reviews · 2021Review
- Safety of a NovelFrontiers in cellular and infection microbiology · 2021Article
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Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Oral delivery of macromolecular drugs is the most patient-preferred route of administration because it is painless and convenient. Over the past 30 years, significant attention has been paid to oral protein delivery in adults. Unfortunately, there is an outstanding need for similar efforts in infants, a patient population with distinct intestinal physiology and treatment needs. Here, we assess the intestinal permeability of neonatal and infant mice to determine the feasibility of orally delivering peptide and protein drugs without permeation enhancers or other assistance. Using the non-everted gut sac model, we found that macromolecular permeability depended on molecular size, mouse age, and intestinal tissue type using model dextrans. For example, the apparent permeability of 70 kDa FITC-Dextran (FD70) in infant small intestinal tissue was 2-5-fold higher than in adult tissue. As mice aged, the expression of barrier-forming and pore-forming tight junction proteins increased and decreased, respectively. The in vivo oral absorption of 4 kDa FITC-Dextran (FD4) and FD70 was significantly higher in younger mice, and there was a fourfold increase in oral absorption of the 80 kDa protein lactoferrin compared to adults. Oral gavage of insulin (5 IU/kg) reduced blood glucose levels in infants by >20% at 2 and 3 h but had no effect in adults. Oral insulin had 35% and <1% of the pharmacodynamic effect of a 1 IU/kg subcutaneous dose in infants and adults, as measured by area above the curve. These data indicate that the uniquely leaky nature of the infantile intestine may support the oral delivery of biologics without the need for traditional oral delivery technology.
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Registered trials
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