ArticleBiomaterials research2023
Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery.
Article in Biomaterials research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Emerging Technologies for Oral Peptide Delivery: From Bioinspired Systems to Smart Device-Assisted Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Strategies for overcoming multiple barriers of oral administration of protein and peptide therapeutics.Materials today. Bio · 2026Review
- Strategies to Improve the Lipophilicity of Hydrophilic Macromolecular Drugs.Advanced healthcare materials · 2026Review
- Research Progress on the Mechanism of Bile Acids and Their Receptors in Depression.International journal of molecular sciences · 2025Review
- Preparation and Therapeutic Evaluation of Engineered Semaglutide and Statin-Lipid Conjugate-Based Nanoparticle.Pharmaceutics · 2025Article
- A Self-Assembling Senolytic Prodrug with Enhanced Bioavailability and Selective Activation for Targeting Senescent Retinal Pigment Epithelium.Biomaterials research · 2025Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDespite the effectiveness of glucagon-like peptide-1 agonist (GLP-1A) in the treatment of diabetes, its large molecular weight and high hydrophilicity result in poor cellular permeability, thus limiting its oral bioavailability. To address this, we developed a chimeric GLP-1A that targets transporter-mediated endocytosis to enhance cellular permeability to GLP-1A by utilizing the transporters available in the intestine, particularly the apical sodium-dependent bile acid transporter (ASBT).
methodsIn silico molecular docking and molecular dynamics simulations were used to investigate the binding interactions of mono-, bis-, and tetra-deoxycholic acid (DOCA) (monoDOCA, bisDOCA, and tetraDOCA) with ASBT. After synthesizing the chimeric GLP-1A-conjugated oligomeric DOCAs (mD-G1A, bD-G1A, and tD-G1A) using a maleimide reaction, in vitro cellular permeability and insulinotropic effects were assessed. Furthermore, in vivo oral absorption in rats and hypoglycemic effect on diabetic db/db mice model were evaluated.
resultsIn silico results showed that tetraDOCA had the lowest interaction energy, indicating high binding affinity to ASBT. Insulinotropic effects of GLP-1A-conjugated oligomeric DOCAs were not different from those of GLP-1A-Cys or exenatide. Moreover, bD-G1A and tD-G1A exhibited improved in vitro Caco-2 cellular permeability and showed higher in vivo bioavailability (7.58% and 8.63%) after oral administration. Regarding hypoglycemic effects on db/db mice, tD-G1A (50 μg/kg) lowered the glucose level more than bD-G1A (50 μg/kg) compared with the control (35.5% vs. 26.4%).
conclusionGLP-1A was conjugated with oligomeric DOCAs, and the resulting chimeric compound showed the potential not only for glucagon-like peptide-1 receptor agonist activity but also for oral delivery. These findings suggest that oligomeric DOCAs can be used as effective carriers for oral delivery of GLP-1A, offering a promising solution for enhancing its oral bioavailability and improving diabetes treatment.
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