ArticleProceedings of the National Academy of Sciences of the United States of America2018
Ionic liquids for oral insulin delivery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 357 citations in OpenAlex.
- Tissue Response to Subcutaneous Infusion Catheter.Journal of diabetes science and technology · 2020Pooled it
- Re-engineering insulin for oral delivery: structural modifications, advanced formulation strategies, and future directions.Drug delivery · 2026Review
- Molecular Evaluation of Deep Eutectic Solvents for Wet Algae Lipid Extraction and Biofuel Production.ACS omega · 2026Article
- Buccal Insulin Delivery Systems: Formulation Approaches, Stability Constraints, and Translational Prospects.Pharmaceutics · 2026Review
- A self-unfolding polymer foil loaded with a permeation enhancer Ionogel for superior oral peptide delivery.Drug delivery and translational research · 2026Article
- Piperazine-Functionalized Nanoparticles Enable Oral Insulin Delivery in Obese Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Deep eutectic solvents@enteric technology for orally delivering anticoagulant macromolecule drug.Acta pharmaceutica Sinica. B · 2026Article
- Ionic Liquids as Interfacial Media for Metal-Free Electrochemical COACS sustainable chemistry & engineering · 2026Article
- Review
- Article
- Oral Treatment of Obesity by GLP-1 and Its Analogs.Pharmaceutics · 2025Review
- Nanoparticle-Based Oral Insulin Delivery: Challenges, Advances, and Future Directions.Pharmaceutics · 2025Review
- Butyrate-based ionic liquid for improved oral bioavailability and synergistic anti-colorectal cancer activity of glycyrol.Journal of pharmaceutical analysis · 2025Article
- Permeation Enhancer-based Ionogel Shows Remarkable Potential for Oral Insulin Delivery.Advanced healthcare materials · 2025Article
- Hydrophobicity-Driven Enhancement of Hydrogen Bonding in Ionic Liquid Hybrid Solvents.The journal of physical chemistry. B · 2025Article
- Impact of Permeation Enhancers on the Release of Insulin from Tablets in Biorelevant Media.Molecular pharmaceutics · 2025Article
- Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats.Scientific reports · 2025Article
- Influence of Choline-Based Ionogel on Transdermal Delivery of Vancomycin Hydrochloride.Molecular pharmaceutics · 2025Article
- Barriers and Strategies for Oral Peptide and Protein Therapeutics Delivery: Update on Clinical Advances.Pharmaceutics · 2025Review
- An Overview on the Role of Ionic Liquids and Deep Eutectic Solvents in Oral Pharmaceuticals.Pharmaceutics · 2025Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.
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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.