In vitro characterisation of a nasal spray comprising an extremely potent human monoclonal antibody

Irene Rossi¹, Manuele Biazzo², Christian Duchow², Jagdeep Shur¹, Antonia Zapata del Baño¹, Chloe Szeto¹, Jlenia Brunetti³, Luisa Bracci³, Ida Paciello⁴, Emanuele Andreano⁴ & Rino Rappuoli^4,5

¹Nanopharm Ltd, An Aptar Pharma Company, Grange Road, Cwmbran NP44 3WY, United Kingdom

²The BioArte Limited, Valletta Road, Mosta, MST 9012, Malta

³MedBiotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Via Aldo Moro 2, Siena 53100, Italy

⁴Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena 53100, Italy

⁵Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy

 Summary

MAD0004J08 was identified between 453 neutralising antibodies (mAb) from 14 COVID-19 recovered patients as the most potent against SARS-CoV-2. A single dose of MAD0004J08 administered intramuscularly (i.m.) showed to induce extremely high serum neutralisation titres against SARS-CoV-2 and its variants of concern.  Inhaled air is primarily routed through the nose, representing the principal port of entry for the virus. For this reason, interest in nasal delivery has increased, especially to deliver mAbs. The aim of this study was to re-design MAD0004J08 formulation used for i.m. administration to exploit nasal delivery. A chitosan/polysorbate formulation platform already applied to another immunoglobulin was employed in combination with Aptar CPS preservative-free nasal pump. A suitable formulation for nasal delivery was obtained, as indicated by pH (6.24) and osmolality (303 mOsm/kg) measured. Formulation process did not impact the size or percentage of the dimeric fraction of the mAb. Droplet size distribution (D_v50 > 50 µm) reported a likely deposition of the formulation in the anterior-middle region of the nose, whereas the chitosan positive charge ensures mucoadhesion and, therefore, will help obtaining a prolonged presence of MAD0004J08. Viscosity of the final nasal formulation (3.3 cP) showed to influence spray pattern and plume geometry. Finally, a reproducible dose of 816.25 µg of MAD0004J08 was delivered with Aptar CPS preservative-free nasal pump. Binding and neutralisation activity before and after spraying was maintained, highlighting the suitability of this platform for nasal delivery of monoclonal antibodies.

Key Message

A formulation suitable for nasal delivery was prepared for MAD0004J08, a highly potent human antibody against SARS-CoV-2, employing a chitosan platform already applied to other immunoglobulins. MAD0004J08 maintained the same binding and neutralisation activity before and after spraying, highlighting the suitability of the combination device/formulation for nasal delivery of monoclonal antibodies.