PHARMACOKINETIC PROFILE INVESTIGATION OF PULMONARY SEMAGLUTIDE ENGINEERED POWDER

The study highlights that an inhalable formulation of the glucagon-like peptide-1 (GLP-1), semaglutide, could represent a promising alternative to the subcutaneous route. The inhalation route provides rapid systemic absorption while mitigating gastrointestinal degradation typically seen with peptide hormone delivery. This method could enhance patient compliance and outcomes by allowing for more convenient dosing regimens. In the spray drying production our lead formulation candidate was prepared using trehalose and leucine as excipients, as previously described. Production yield was high (> 75%) and the FPF was about 43%. The MTT analysis demonstrated that the semaglutide peptide is non-toxic to A549 cell lines at concentrations up to 64 lg/mL. Pharmacokinetic (PK) studies in rats revealed distinct absorption profiles, with intratracheal (IT) administration yielding a maximum concentration (Cmax) of 0.341 lg/mL at 3 hours, whereas subcutaneous (SC) administration resulted in a Cmax of 0.406 lg/mL at 4 hours. Even though, the AUC of the IT administered lead spray dried candidate was about 20% of what observed for the peptide SC administration, SMG was promptly absorbed through the lungs and the data set collected was in line with what reported in other recent works.