ArticleNature communications2025
Permeation enhancer-induced membrane defects assist the oral absorption of peptide drugs.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
9 citing papers in PubMed.
- Salcaprozate Sodium as a Permeation Enhancer-Mechanism, Applications and Unresolved Questions.Pharmaceutics · 2026Review
- Semaglutide Bioavailability: Limitations, Formulation Innovation and Future Opportunities.Pharmaceutical research · 2026Review
- Emerging Technologies for Oral Peptide Delivery: From Bioinspired Systems to Smart Device-Assisted Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Oral GLP-1-Based Therapeutics in the Obesity-Metabolic Syndrome-Diabetes Continuum: Translational Advances, Clinical Barriers, and Emerging Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Navigating the complexity of oral peptide delivery: challenges and strategies to enhance oral bioavailability.Frontiers in drug delivery · 2026Review
- Structure-Based Modeling of Environment-Dependent Protonation States Across LNP Formulations with Atomistic CpHMD.Molecular pharmaceutics · 2025Article
- Challenges and opportunities in computational studies for lipid nanoparticle development.npj drug discovery · 2025Review
- Oral absorption of semaglutide: pharmacokinetic modeling and molecular dynamics simulations.In silico pharmacology · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
The passive membrane permeation of small-molecule drugs and small hydrophobic peptides is relatively well understood. In contrast, how long polar peptides can pass through a membrane has remained a mystery. This process can be achieved with permeation enhancers, contributing significantly to the oral transcellular absorption of important peptide drugs like semaglutide - the active pharmaceutical ingredient in Ozempic, which is used as Rybelsus in a successful oral formulation. Here we now provide a detailed, plausible molecular mechanism of how such a polar peptide can realistically pass through a membrane paired with the permeation enhancer salcaprozate sodium (SNAC). We provide both simulation results, obtained with scalable continuous constant pH molecular dynamics (CpHMD) simulations, and experimental evidence (NMR, DOSY, and DLS) to support this unique permeation mechanism. Our combined evidence points toward the formation of permeation-enhancer-filled, fluid membrane defects, in which the polar peptide can be submerged in a process analogous to quicksand.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.