ArticleProceedings of the National Academy of Sciences of the United States of America2022
The strawberry-derived permeation enhancer pelargonidin enables oral protein delivery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- In Vitro Testing of Artificial Sweeteners with Apple and Chokeberry Fruit Juice Extracts for Intestinal Permeability and Glucose Uptake.ACS omega · 2026Article
- Strategies for overcoming multiple barriers of oral administration of protein and peptide therapeutics.Materials today. Bio · 2026Review
- Extended local anesthesia enabled by flavonoid permeation enhancers.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Navigating the complexity of oral peptide delivery: challenges and strategies to enhance oral bioavailability.Frontiers in drug delivery · 2026Review
- Food-derived molecules as regulators of intestinal tight junctions and barrier function: mechanisms and implications.Frontiers in drug delivery · 2026Review
- 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
- Pelargonidin improves functional recovery and attenuates neuropathic pain following spinal cord injury in rats: relevance to its neuroprotective, antioxidant, and anti-inflammatory effects.Frontiers in pharmacology · 2025Article
- Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC - What is Coming Next?Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Nanostructure-Mediated Transport of Therapeutics through Epithelial Barriers.International journal of molecular sciences · 2024Review
- Proof-of-concept studies with a computationally designed MProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Recent advances in oral insulin delivery technologies.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Sweet Cherry Extract as Permeation Enhancer of Tyrosine Kinase Inhibitors: A Promising Prospective for Future Oral Anticancer Therapies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Storming the gate: New approaches for targeting the dynamic tight junction for improved drug delivery.Advanced drug delivery reviews · 2023Review
- Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin.Biomaterials · 2023Article
- Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems.Nature reviews. Drug discovery · 2023Review
- Preparation, Drug Distribution, and In Vivo Evaluation of the Safety of Protein Corona Liposomes for Liraglutide Delivery.Nanomaterials (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Although patients generally prefer oral drug delivery to injections, low permeability of the gastrointestinal tract makes this method impossible for most biomacromolecules. One potential solution is codelivery of macromolecules, including therapeutic proteins or nucleic acids, with intestinal permeation enhancers; however, enhancer use has been limited clinically by modest efficacy and toxicity concerns surrounding long-term administration. Here, we hypothesized that plant-based foods, which are well tolerated by the gastrointestinal tract, may contain compounds that enable oral macromolecular absorption without causing adverse effects. Upon testing more than 100 fruits, vegetables, and herbs, we identified strawberry and its red pigment, pelargonidin, as potent, well-tolerated enhancers of intestinal permeability. In mice, an oral capsule formulation comprising pelargonidin and a 1 U/kg dose of insulin reduced blood glucose levels for over 4 h, with bioactivity exceeding 100% relative to subcutaneous injection. Effects were reversible within 2 h and associated with actin and tight junction rearrangement. Furthermore, daily dosing of mice with pelargonidin for 1 mo resulted in no detectable side effects, including weight loss, tissue damage, or inflammatory responses. These data suggest that pelargonidin is an exceptionally effective enhancer of oral protein uptake that may be safe for routine pharmaceutical use.
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Registered trials
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