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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.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.4155/tde.14.117
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.4155/TDE.14.117
Acknowledgements
The authors are grateful to L Perrino, PhD (Physiology and Biophysics) of the VCU School of Medicine for technical assistance on the brain immunohistochemistry.
Financial & competing interests disclosure
This research was funded by the Jeffress Memorial Trust of Virginia and the VCU School of Pharmacy. PP Nadkarni acknowledges the financial support from the VCU School of Pharmacy and the VCU Graduate Dissertation Assistantship during graduate study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.