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Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability

The lipid nanoparticle (LNP) is one of the promising nanotechnologies for the delivery of RNA molecules, such as small interfering RNA (siRNA) and messenger RNA (mRNA). A series of LNPs that contain an mRNA encoding the antigen protein of SARS-CoV-2 were already approved as RNA vaccines against this...

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Autores principales: Shirane, Daiki, Tanaka, Hiroki, Sakurai, Yu, Taneichi, Sakura, Nakai, Yuta, Tange, Kota, Ishii, Itsuko, Akita, Hidetaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383539/
https://www.ncbi.nlm.nih.gov/pubmed/37514007
http://dx.doi.org/10.3390/pharmaceutics15071819
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author Shirane, Daiki
Tanaka, Hiroki
Sakurai, Yu
Taneichi, Sakura
Nakai, Yuta
Tange, Kota
Ishii, Itsuko
Akita, Hidetaka
author_facet Shirane, Daiki
Tanaka, Hiroki
Sakurai, Yu
Taneichi, Sakura
Nakai, Yuta
Tange, Kota
Ishii, Itsuko
Akita, Hidetaka
author_sort Shirane, Daiki
collection PubMed
description The lipid nanoparticle (LNP) is one of the promising nanotechnologies for the delivery of RNA molecules, such as small interfering RNA (siRNA) and messenger RNA (mRNA). A series of LNPs that contain an mRNA encoding the antigen protein of SARS-CoV-2 were already approved as RNA vaccines against this infectious disease. Since LNP formulations are generally metastable, their physicochemical properties are expected to shift toward a more stable state during the long-time storage of suspensions. The current mRNA vaccines are supplied in the form of frozen formulations with a cryoprotectant for preventing deterioration. They must be stored in a freezer at temperatures from −80 °C to −15 °C. It is thought that therapeutic applications of this mRNA-LNP technology could be accelerated if a new formulation that permits mRNA-LNPs to be stored under milder conditions were available. We previously reported on a one-pot method for producing siRNA-encapsulated LNPs by combining freeze-drying technology with the conventional alcohol dilution method (referred to herein as the “alcohol dilution–lyophilization method”). In this study, this method was applied to the preparation of mRNA-LNPs to provide a freeze-dried formulation of mRNA LNPs. The resulting formulation can be stored at 4 °C for at least 4 months.
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spelling pubmed-103835392023-07-30 Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability Shirane, Daiki Tanaka, Hiroki Sakurai, Yu Taneichi, Sakura Nakai, Yuta Tange, Kota Ishii, Itsuko Akita, Hidetaka Pharmaceutics Article The lipid nanoparticle (LNP) is one of the promising nanotechnologies for the delivery of RNA molecules, such as small interfering RNA (siRNA) and messenger RNA (mRNA). A series of LNPs that contain an mRNA encoding the antigen protein of SARS-CoV-2 were already approved as RNA vaccines against this infectious disease. Since LNP formulations are generally metastable, their physicochemical properties are expected to shift toward a more stable state during the long-time storage of suspensions. The current mRNA vaccines are supplied in the form of frozen formulations with a cryoprotectant for preventing deterioration. They must be stored in a freezer at temperatures from −80 °C to −15 °C. It is thought that therapeutic applications of this mRNA-LNP technology could be accelerated if a new formulation that permits mRNA-LNPs to be stored under milder conditions were available. We previously reported on a one-pot method for producing siRNA-encapsulated LNPs by combining freeze-drying technology with the conventional alcohol dilution method (referred to herein as the “alcohol dilution–lyophilization method”). In this study, this method was applied to the preparation of mRNA-LNPs to provide a freeze-dried formulation of mRNA LNPs. The resulting formulation can be stored at 4 °C for at least 4 months. MDPI 2023-06-26 /pmc/articles/PMC10383539/ /pubmed/37514007 http://dx.doi.org/10.3390/pharmaceutics15071819 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shirane, Daiki
Tanaka, Hiroki
Sakurai, Yu
Taneichi, Sakura
Nakai, Yuta
Tange, Kota
Ishii, Itsuko
Akita, Hidetaka
Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability
title Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability
title_full Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability
title_fullStr Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability
title_full_unstemmed Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability
title_short Development of an Alcohol Dilution–Lyophilization Method for the Preparation of mRNA-LNPs with Improved Storage Stability
title_sort development of an alcohol dilution–lyophilization method for the preparation of mrna-lnps with improved storage stability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383539/
https://www.ncbi.nlm.nih.gov/pubmed/37514007
http://dx.doi.org/10.3390/pharmaceutics15071819
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