Translating a Thin-Film Rehydration Method to Microfluidics for the Preparation of a SARS-CoV-2 DNA Vaccine: When Manufacturing Method Matters
Issued Date
2022-07-01
Resource Type
eISSN
19994923
Scopus ID
2-s2.0-85133735685
Journal Title
Pharmaceutics
Volume
14
Issue
7
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pharmaceutics Vol.14 No.7 (2022)
Suggested Citation
Peletta A., Prompetchara E., Tharakhet K., Kaewpang P., Buranapraditkun S., Yostrerat N., Manopwisedjaroen S., Thitithanyanont A., Avaro J., Krupnik L., Neels A., Ruxrungtham K., Ketloy C., Borchard G. Translating a Thin-Film Rehydration Method to Microfluidics for the Preparation of a SARS-CoV-2 DNA Vaccine: When Manufacturing Method Matters. Pharmaceutics Vol.14 No.7 (2022). doi:10.3390/pharmaceutics14071427 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/87577
Title
Translating a Thin-Film Rehydration Method to Microfluidics for the Preparation of a SARS-CoV-2 DNA Vaccine: When Manufacturing Method Matters
Other Contributor(s)
Abstract
Previous investigations conducted on a liposomal formulation for a SARS-CoV-2 DNA vaccine manufactured using the thin-film layer rehydration method showed promising immunogenicity results in mice. The adaptation of the liposomal formulation to a scalable and reproducible method of manufacture is necessary to continue the investigation of this vaccine candidate. Microfluidics manufacture shows high potential in method translation. The physicochemical characterization of the blank liposomes produced by thin-film layer rehydration or microfluidics were shown to be comparable. However, a difference in lipid nanostructure in the bilayer resulted in a significant difference in the hydration of the thin-film liposomes, ultimately altering their complexation be-havior. A study on the complexation of liposomes with the DNA vaccine at various N/P ratios showed different sizes and Zeta-potential values between the two formulations. This difference in the complexation behavior resulted in distinct immunogenicity profiles in mice. The thin-film layer rehydration-manufactured liposomes induced a significantly higher response compared to the microfluidics-manufactured samples. The nanostructural analysis of the two samples revealed the critical importance of understanding the differences between the two formulations that resulted in the different immunogenicity in mice.