Nodexen (exenatide oral) / NOD Pharm - LARVOL DELTA

Unlocking the potential of microfluidic assisted formulation of exenatide-loaded solid lipid nanoparticles. (PubMed, Int J Pharm) - "Oral exenatide has low bioavailability due to poor gastrointestinal stability and absorption. However, the exenatide delivery with 10 w/w% PEGylated SLN across mucus-producing Caco-2/HT29-MTX coculture layer was 2-fold higher compared to the unformulated peptide, and 1.5 higher than non-PEGylated SLN. The 30 w/w% SLN PEGylation did not improve the peptide transport neither through Caco-2 cell monolayers nor through Caco-2/HT29-MTX coculture layer."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Double layer spherical Nanoparticles with Hyaluronic Acid Coating to Enhance Oral Delivery of Exenatide in T2DM rats. (PubMed, Eur J Pharm Biopharm) - "HA coating enhanced the adhesion of nanoparticles (NPs), and RMs-O/W-HA increased cellular uptake through CD44-mediated endocytosis. Pharmacodynamics results showed that RMs-SEDDS and RMs-O/W-HA could reduce blood glucose in type 2 diabetic rats, protect pancreatic β cells to a certain extent, and relieve insulin resistance and hyperlipemia complications with good safety."

Journal • Preclinical • Diabetes • Type 2 Diabetes Mellitus

Oral Delivery of a GLP-1 Agonist with High Bioavailability in Dogs and Humans (ADA 2023) - "While most require injections due to poor oral bioavailability, Rybelsus® (semaglutide) is orally effective for glycemic control, however, its 1% bioavailability and high dose requirement limits its viability as an effective oral weight-loss medication...Awake dogs received 10 µg of exenatide orally via RP (RT-104, N=4) or SC injection (Byetta®, N=5), while 5 healthy human volunteers received 10 µg of Byetta® via an endoscopic, transenteric injection and, after a 3-day washout, via a SC injection. Exenatide concentrations, determined via ELISA in serially collected plasma samples, yielded similar PK curves in both species (Figure) with oral bioavailability via RP or endoscopic injection calculated to be 79% in dogs and 81% in humans, respectively, compared to SC injections. These data provide the basis for further development of an orally ingestible GLP-1 mimetic (RT-104) which would provide the higher, efficacious exposures needed for both..."

Late-breaking abstract • Metabolic Disorders

Characterization of the physicochemical interactions between exenatide and two intestinal permeation enhancers: sodium caprate (C) and salcaprozate sodium (SNAC). (PubMed, Int J Pharm) - "In biorelevant intestinal media, the bile salts in FaSSIF and FeSSIF further reduced the binding of both agents to exenatide (K ≈ 100 µM), indicating that the interaction between the PEs and exenatide might be inhibited by bile salts in the GI lumen. This study suggests that the interactions of both PEs with exenatide follow a similar non-covalent mechanism and are of low affinity."

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Effective oral delivery of Exenatide-Zn complex through distal ileum-targeted double layers nanocarriers modified with deoxycholic acid and glycocholic acid in diabetes therapy. (PubMed, Biomaterials) - "At present, oral Exenatide is not available on the market and therefore the relevant studies are valuable. As a result, this dual cholic acid-functionalized nanoparticle demonstrated enhanced uptake and transport of Exenatide, and a special targeting to apical sodium-dependent cholic acid transporter in vitro. Moreover, in vivo studies showed that the nanoparticle effectively accumulated in distal ileum, raised the plasma concentration of Exenatide, prolonged hypoglycemic effect, reduced blood lipid levels, and lightened organ lesions."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice. (PubMed, J Nanobiotechnology) - "Both COM NPs and DIS NPs are promising systems for oral delivery of exenatide, and COM NPs are better in blood glucose level control than DIS NPs. Using prolamin to produce multifunctional nanoparticles for oral delivery of peptide drug by hydrophobic interaction is a simple and effective strategy."

Journal • Preclinical • Diabetes • Gastrointestinal Disorder • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice. (PubMed, Sci Rep) - "To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Fluorescence-labeled NPs were used to investigate the effects of Fc targeting, and the results demonstrated that the NPs-Fc stayed in the gastrointestinal tract for a longer time in comparison with the unmodified NPs, as shown by the whole-body fluorescence images and fluorescence images of the dissected organs detected by in vivo imaging in live mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral peptide/protein drug delivery."

Journal • Preclinical • Biosimilar

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery. (PubMed, Eur J Pharm Biopharm) - "Furthermore, orally administered exenatide-THA and exenatide-DOC NCs in healthy rats resulted in a relative bioavailability of 27.96 ± 5.24% and 16.29 ± 6.63%, respectively, confirming the comparatively higher potential of the cationic surfactant over the anionic surfactant. Findings of this work highlight the potential of the type of counterion used for HIP as key to successful design of lipid-based NCs for oral exenatide delivery."

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