Pan, HW;
Guo, J;
Zhu, L;
Leung, SWS;
Zhang, C;
Lam, JKW;
(2023)
Enhanced powder dispersion of dual-excipient spray-dried powder formulations of a monoclonal antibody and its fragment for local treatment of severe asthma.
International Journal of Pharmaceutics
, 644
, Article 123272. 10.1016/j.ijpharm.2023.123272.
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Abstract
The advent of biologics has brought renewed hope for patients with severe asthma, a condition notorious for being hampered by poor response to conventional therapies and adverse drug reactions owing to corticosteroid dependence. However, biologics are administered as injections, thereby precluding the benefits inhalation therapy could offer such as increased bioavailability at the site of action, minimal systemic side effects, non-invasiveness, and self-administration. Here, 2-hydroxypropyl-beta-cyclodextrin and ʟ-leucine were co-spray-dried, as protein stabiliser and dispersion enhancer, respectively, at various weight ratios to produce a series of formulation platforms. Powder aerosolisation characteristics and particle morphology were assessed for suitability for pulmonary delivery. The selected platform with the best aerosol performance, a 1:1 ratio of the excipients, was then incorporated with a monoclonal antibody directed against IL-4 receptor alpha or its antigen-binding fragment. The dual-excipient antibody formulations exhibited emitted fraction of at least 80% and fine particle fraction exceeding 60% in cascade impactor study, while the residual moisture content was within a desirable range between 1% and 3%. The in vitro antigen-binding ability and inhibitory potency of the spray-dried antibody were satisfactorily preserved. The results from this study corroborate the viability of inhaled solid-state biomacromolecules as a promising treatment approach for asthma.
| Type: | Article |
|---|---|
| Title: | Enhanced powder dispersion of dual-excipient spray-dried powder formulations of a monoclonal antibody and its fragment for local treatment of severe asthma |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ijpharm.2023.123272 |
| Publisher version: | https://doi.org/10.1016/j.ijpharm.2023.123272 |
| Language: | English |
| Additional information: | Copyright © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Antibody fragment, Asthma, Cyclodextrin, Inhalation, Leucine, Pulmonary delivery, Spray drying |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10175758 |
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