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http://hdl.handle.net/11375/27470
Title: | Effect of shear stresses on adenovirus activity and aggregation during atomization to produce thermally stable vaccines by spray drying |
Authors: | Morgan, Blair |
Department: | Chemical Engineering |
Publication Date: | 1-Jun-2020 |
Publisher: | ACS Biomaterials Science and Engineering |
Abstract: | Considering the substantive potential benefits of thermally stable dry powder vaccines to public health, causes for inactivation of their sensitive viral vectors during preparation require intensive study. The focus of this work was atomization of solutions containing encapsulating excipients and a human type 5 adenovirus, involving a detailed investigation of shear stresses in the nozzle of a spray dryer. Samples were sprayed at 25 °C into falcon tubes and immediately evaluated for viral activity by in vitro testing, minimizing the confounding of thermal effects on the deactivation of the virus. Despite expectations of only virus deactivation with ever-increasing shear stresses in the spray nozzle, some conditions were found to show better activity than the positive control, leading to investigations of viral aggregation. It was found that the adenovirus experienced minor aggregation when mixed with the excipient solutions, which was reversed by subjecting samples to moderate shear conditions. At very high shear rates, activity diminished again due to damage to the viral capsid, which also led to the production of new aggregates after atomization. Despite these findings, activity losses caused by shear were small compared to the overall spray drying process. However, formulation composition, solution viscosity and process conditions should be considered carefully for medicinal optimization due to their impact on aggregation. This is the first known report comparing shear, aggregation, and biologic activity loss during the atomization step of spray drying thermally stable viral vaccines. |
URI: | http://hdl.handle.net/11375/27470 |
Identifier: | https://doi.org/10.1021/acsbiomaterials.0c00317 |
Appears in Collections: | Faculty Publications |
Files in This Item:
File | Description | Size | Format | |
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Effect of atomization shear on viral vector activity manucsript BM v11_EC.pdf | 6.48 MB | Adobe PDF | View/Open |
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