ACS applied materials & interfacesMay 1, 2026

Improved Oral Delivery of Semaglutide for Type 2 Diabetes Using an Ionic Liquid-Based Coating

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated May 2, 2026

Abstract

A 2.3-fold increase in maximum plasma concentration of semaglutide was observed with the new formulation.

An enteric solid formulation using sorbic acid-choline ionic liquids was developed for oral delivery of semaglutide.
The formulation showed strong resistance to acidic conditions and facilitated pH-responsive release in simulated intestinal fluid.
Imaging studies indicated prolonged retention of the IL-loaded enteric particles in the intestine.
In type 2 diabetes mellitus mice, the new formulation demonstrated glucose-lowering effects similar to those of subcutaneous semaglutide administration.
Repeated-dose studies suggested favorable tolerability of the formulation in both systemic and gastrointestinal contexts.

Simplified

Oral delivery of peptide therapeutics remains challenging due to gastrointestinal degradation, poor epithelial permeability, and extremely low bioavailability. To address these limitations, we developed an enteric solid formulation based on sorbic acid-choline ionic liquids (ILs) for the oral delivery of semaglutide (Sema), a glucagon-like peptide-1 (GLP-1) analogue. The IL-based enteric system was designed to enhance peptide stability, reduce gastric degradation, and promote intestinal absorption.studies demonstrated strong resistance to acidic conditions and pH-responsive release in simulated intestinal fluid.imaging further revealed prolonged intestinal retention of the IL-loaded enteric particles. Pharmacokinetic evaluation showed a 2.3-fold increase in maximum plasma concentration compared to the reference Rybelsus. In type 2 diabetes mellitus (T2DM) mice, the formulation achieved glucose-lowering efficacy comparable to subcutaneous Sema administration, with additional improvements in hepatic histology. Importantly, repeated-dose studies indicated favorable systemic and gastrointestinal tolerability under the tested conditions. Collectively, these results demonstrate that IL-based enteric formulation enhances oral peptide exposure while maintaining safety, offering a promising strategy for noninvasive T2DM management. In vitro In vivo

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Improved Oral Delivery of Semaglutide for Type 2 Diabetes Using an Ionic Liquid-Based Coating

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