Hydrophobic ion-paired semaglutide in self-emulsifying system enhances oral delivery, cutting glucose in diabetic rats.

Type 2 diabetes management often relies on GLP-1 receptor agonists like semaglutide, which offer potent glycemic control. However, current injectable formulations face patient compliance issues, while existing oral tablets struggle with low bioavailability due to semaglutide's inherent hydrophilicity and susceptibility to enzymatic degradation in the gastrointestinal tract. This limits therapeutic efficacy and patient convenience, highlighting a critical need for novel oral delivery strategies that overcome these biopharmaceutical barriers.

Researchers developed an oral delivery system for semaglutide, forming a hydrophobic ion pair (HIP) with sodium docusate (SET-DOC). This was then incorporated into a self-emulsifying drug delivery system (SD@SEDDS). In vitro, they characterized SD@SEDDS for particle size, drug loading, and stability. Permeability and P-glycoprotein efflux were assessed using a Caco-2/HT-29 co-culture model. In vivo, SD@SEDDS was orally administered to a type 2 diabetic rat model to evaluate blood glucose, lipid profiles, and biocompatibility.

The optimized SD@SEDDS formulation successfully produced a clear emulsion upon dilution, exhibiting a uniform particle size of 85.55 nm and a high drug loading of 2.64 mg/g, alongside excellent stability.

In vitro transport studies using a Caco-2/HT-29 co-culture model demonstrated significantly enhanced permeability and a notable reduction in P-glycoprotein-mediated efflux, suggesting improved absorption potential. In vivo, oral administration of SD@SEDDS to a type 2 diabetic rat model led to a significant reduction in blood glucose levels. Furthermore, the treatment improved lipid profiles, indicating broader metabolic benefits. Importantly, the formulation exhibited good biocompatibility with no observable toxicity, supporting its safety profile in this preclinical model.