Characterisation of a Human Nasal Spray for Nose to Brain Delivery of Insulin

Jed Wingrove1, Magda Swedrowska3, Mark Parry2, Mervin Ramjeeawon2, David Taylor3, Gregoire Gauthier4, Fernando Zelaya1, Ben Forbes3

1King’s College London, Institute of Psychiatry, Psychology & Neuroscience, London SE5 8AF, UK

2Intertek-Melbourn, Melbourn SG8 6DN, UK

3King’s College London, Institute of Pharmaceutical Science, London SE1 9NH, UK

4Nemera, La Verpillière 38292, France

Summary
Giving the increased prevalence of insulin-related metabolic disorders, such as diabetes and obesity in the developed western world there is a desired interest in understanding the effects of insulin within the central nervous system. Intranasal insulin administration, which takes advantage of the nose to brain pathway can increase insulin concentrations within the brain, whilst limiting systemic insulin effects. However, this route offers substantial obstacles and requires a device capable of producing posterior-superior nasal cavity drug deposition. In this study, using 400IU/ml insulin solution, we ran three nasal pump-actuator configurations through an analytical characterisation pipeline to measure droplet size distribution, plume geometry and spray pattern. We compared the measured parameters, to literature based a priori defined parameters recommended for increased posterior nasal cavity deposition. The pump which best matched these defined parameters was then used for a functional magnetic resonance imaging (fMRI) study in healthy volunteers to assess the effects of intranasal insulin on food reward and appetite regulation.