Pulmonary delivery of anorectic oxyntomodulin in rats: food intake suppression, reduced body weight gain and pharmacokinetics

Abstract

Background: Oxyntomodulin (OXM1–37) is an anorectic gut-secreting peptide with a promise to treat obesity, but its needle-free delivery has yet to be successful. Results: Pulmonary delivery of OXM1–37, but not its C-terminal octapeptides, caused dose-related, transient 4–6 h food intake suppression in rats. At 0.5 mg/kg, its 30–38% food intake suppression led to 46% reduction in body weight gain by day 8. Its lung absorption was fast, elevating the systemic level rapidly, yet the bioavailability was low at 13%. In the brain, twofold neuronal c-fos activation was seen in the hypothalamus arcuate nucleus and brainstem area postrema. Conclusion: Pulmonary delivery is a promising needle-free systemic delivery option for OXM1–37 to treat obesity, as enabling effective lung absorption and brain interaction.