Self-Emulsifying delivery systems for oral administration of exenatide: Hydrophobic ion pairs vs. Dry reverse micelles.

This research provides a comparative analysis of two innovative strategies - hydrophobic ion pairing (HIP) and dry reverse micelles (dRM) - to enhance the oral bioavailability of exenatide, a GLP-1 receptor agonist, as a diabetes treatment. These techniques were integrated into self-emulsifying drug delivery systems (SEDDS) featuring a lipid matrix composed of propylene glycol dilaurate and salicylic acid methyl ester (32.5 %:32.5 %; v/v) with polyethoxylated-35 castor oil (35 %; v/v) as surfactant. HIP enhances the lipophilicity of exenatide through ion-pairing with cationic surfactants, thereby promoting efficient incorporation into the lipid matrix of SEDDS. In contrast, dRM forms stabilized micellar structures using sorbitan monooleate, improving safety and compatibility. The droplet sizes for SEDDS were analyzed via dynamic light scattering and varied from 95 to 110 nm, with a polydispersity index of approximately 0.25, and zeta potentials between -1 mV and -6 mV. The maximum log D values were 2.13 ± 0.31 for exenatide-loaded HIPs (ExeHIP) and 2.05 ± 0.08 for exenatide-loaded dRM (ExedRM), indicating sufficient lipophilicity, which is crucial for effective absorption and bioavailability. Toxicological assessments showed low toxicity levels. In vivo studies indicated a relative bioavailability of 18.08 % for ExeHIP and 17.06 % for ExedRM compared to intravenous injection. Both strategies demonstrated a similar potential in relative bioavailability, reflecting a significant increase in bioavailability compared to the control. Notably, the HIP formulation provided better control over exenatide release and ensured stable GLP-1 levels, while dRMs are preferable for safety reasons as all excipients have GRAS status and are therefore FDA approved.