Stefania Glieca1, Anna Signor2, Martina Colognesi2, Sara De Martin2, Alessia Morri2, Benedetta Campara2, Eride Quarta1, Aurora Squeri1, Fabio Sonvico1, Irene Rossi3, Ross Blezard4, Andrea Silvestri5, Gianfranco Pasut2 & Francesca Buttini1
1Food and Drug Department, University of Parma, Parco Area delle Scienze 27/a, Parma, 43123, Italy
2 Pharmaceutical and Pharmacological Sciences Department, University of Padova, Via F. Marzolo 5, Padova, 35131, Italy
3Harro Höfliger, Helmholtzstraße 4, Allmersbach im Tal, 71573, Germany
4DFE Pharma, Klever Straße 187, Goch, 47568, Germany
5Sterling Via della Carboneria 30, Corciano, 06073, Perugia, Italy
Summary
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 µg/mL. Pharmacokinetic (PK) studies in rats revealed distinct absorption profiles, with intratracheal (IT) administration yielding a maximum concentration (Cmax) of 0.341 µg/mL at 3 hours, whereas subcutaneous (SC) administration resulted in a Cmax of 0.406 µg/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.