Non-covalent lipidation and self nanoemulsions: Ex-vivo porcine buccal mucosal permeation of GLP-1RA

Oral delivery of GPL-1RAs is challenged by poor oral bioavailability due to their intrinsic physicochemical properties, like high hydrophilicity, high molecular weight, and susceptibility to gastrointestinal degradation (1). Recent optimization efforts employing permeation-enhancer led to approval of oral semaglutide (Rybelsus®), although it has an oral bioavailability of less than 1% (2). Lipo-peptides exhibit enhanced compatibility with self-nanoemulsifying delivery systems (SNEDDS) (3). Our aim was to improve the lipophilicity of GLP-1 and load into SNEDDS for enhanced buccal permeability.