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Spray-Dried and Spray-Freeze-Dried Powder Formulations of an Anti-Interleukin-4Rα Antibody for Pulmonary Delivery

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Abstract

Objective

The therapeutic options for severe asthma are limited, and the biological therapies are all parenterally administered. The purpose of this study was to formulate a monoclonal antibody that targets the receptor for IL-4, an interleukin implicated in the pathogenesis of severe asthma, into a dry powder intended for delivery via inhalation.

Methods

Dehydration was achieved using either spray drying or spray freeze drying, which exposes the thermolabile biomacromolecules to stresses such as shear and adverse temperatures. 2-hydroxypropyl-beta-cyclodextrin was incorporated into the formulation as protein stabiliser and aerosol performance enhancer. The powder formulations were characterised in terms of physical and aerodynamic properties, while the antibody was assessed with regard to its structural stability, antigen-binding ability, and in vitro biological activity after drying.

Results

The spray-freeze-dried formulations exhibited satisfactory aerosol performance, with emitted fraction exceeding 80% and fine particle fraction of around 50%. The aerosolisation of the spray-dried powders was hindered possibly by high residual moisture. Nevertheless, the antigen-binding ability and inhibitory potency were unaffected for the antibody in the selected spray-dried and spray-freeze-dried formulations, and the antibody was physically stable even after one-year storage at ambient conditions.

Conclusions

The findings of this study establish the feasibility of developing an inhaled dry powder formulation of an anti-IL-4R antibody using spray drying and spray freeze drying techniques with potential for the treatment of severe asthma.

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Conflict of Interest

The authors declare no conflict of interest.

Funding

This project was funded by the Seed Funding for Strategic Interdisciplinary Research Scheme, The University of Hong Kong. H.W.P. is a recipient of the Hong Kong PhD Fellowship, Research Grants Council, Hong Kong (PF18-13277).

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR

    Harry W. Pan, Han Cong Seow, Jason C. K. Lo, Susan W. S. Leung & Jenny K. W. Lam

  2. R&D Department, Shanghai MabGeek Biotech Co. Ltd., Room 304, No. 1011 Halei Road, Zhangjiang Hi-tech Park, Shanghai, 201203, People’s Republic of China

    Jinlin Guo, Lingqiao Zhu & Chenghai Zhang

  3. Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, New Territories, Shatin, Hong Kong, SAR

    Jenny K. W. Lam

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  1. Harry W. Pan
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Contributions

This study was conceptualised and designed by J.K.W.L., H.W.P., and J.C.K.L. The experiments and data analyses were performed by H.W.P. The manuscript was written by H.W.P. and edited by H.W.P., H.C.S., S.W.S.L., and J.K.W.L. The antibody was developed by J.G., L.Z., and C.Z. All authors reviewed the manuscript and approved the final version.

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Correspondence to Chenghai Zhang or Jenny K. W. Lam.

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Pan, H.W., Seow, H.C., Lo, J.C.K. et al. Spray-Dried and Spray-Freeze-Dried Powder Formulations of an Anti-Interleukin-4Rα Antibody for Pulmonary Delivery. Pharm Res 39, 2291–2304 (2022). https://doi.org/10.1007/s11095-022-03331-w

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  • DOI: https://doi.org/10.1007/s11095-022-03331-w

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