Preprint Article Version 1 This version is not peer-reviewed

A Novel Method to Prepare Uniform Micro-Sized Dry Powder Formulations, including Aggregation-Controlled VHH Antibodies

Version 1 : Received: 13 October 2024 / Approved: 14 October 2024 / Online: 15 October 2024 (12:10:02 CEST)

How to cite: Moritani, T.; Masaki, H.; Yonehara, R.; Suzuki, T.; Arai, H.; Tsuchiya, M.; Nemoto, N. A Novel Method to Prepare Uniform Micro-Sized Dry Powder Formulations, including Aggregation-Controlled VHH Antibodies. Preprints 2024, 2024101136. https://doi.org/10.20944/preprints202410.1136.v1 Moritani, T.; Masaki, H.; Yonehara, R.; Suzuki, T.; Arai, H.; Tsuchiya, M.; Nemoto, N. A Novel Method to Prepare Uniform Micro-Sized Dry Powder Formulations, including Aggregation-Controlled VHH Antibodies. Preprints 2024, 2024101136. https://doi.org/10.20944/preprints202410.1136.v1

Abstract

The preparation of antibodies in the powder form without changing their physicochemical properties may enable their use in new drug delivery system therapies or for non-refrigerated storage. The variable domain of the heavy chain of heavy chain (VHH) antibodies is more suited for this purpose than conventional antibodies because of their high thermal stability and ability to refold. In this report, the fine droplet drying (FDD) process was selected as the powderization technique because of its favorable features, such as mild drying conditions and the generation of uniform particle sizes. The aggregation, binding, particle and in vitro inhalation properties of the prepared VHH antibody powder (VHHp) were evaluated. The amount of aggregated VHH antibody present in VHHp depended on the flow temperature during the FDD process, with higher temperatures yielding a high aggregation ratio. In contrast, no significant difference in binding activity was observed between each VHHp preparation and the native VHH antibody. Analysis of VHHp samples revealed that the particles were uniformly spherical with a single-micron size. VHHp showed a fine inhalation property in the inhalation property test. These findings suggest that the FDD process affords various VHH antibody powder formulations, including pharmaceutical formulations.

Keywords

nanobody; single-domain antibody; fine droplet drying process; microparticle; inhalable powder; intratracheal administration; inkjet technology

Subject

Biology and Life Sciences, Biology and Biotechnology

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