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Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics

In the recent of years, the use of lipid nanoparticles (LNPs) for RNA delivery has gained considerable attention, with a large number in the clinical pipeline as vaccine candidates or to treat a wide range of diseases. Microfluidics offers considerable advantages for their manufacture due to its sca...

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Autores principales: Roces, Carla B., Lou, Gustavo, Jain, Nikita, Abraham, Suraj, Thomas, Anitha, Halbert, Gavin W., Perrie, Yvonne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697682/
https://www.ncbi.nlm.nih.gov/pubmed/33203082
http://dx.doi.org/10.3390/pharmaceutics12111095
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author Roces, Carla B.
Lou, Gustavo
Jain, Nikita
Abraham, Suraj
Thomas, Anitha
Halbert, Gavin W.
Perrie, Yvonne
author_facet Roces, Carla B.
Lou, Gustavo
Jain, Nikita
Abraham, Suraj
Thomas, Anitha
Halbert, Gavin W.
Perrie, Yvonne
author_sort Roces, Carla B.
collection PubMed
description In the recent of years, the use of lipid nanoparticles (LNPs) for RNA delivery has gained considerable attention, with a large number in the clinical pipeline as vaccine candidates or to treat a wide range of diseases. Microfluidics offers considerable advantages for their manufacture due to its scalability, reproducibility and fast preparation. Thus, in this study, we have evaluated operating and formulation parameters to be considered when developing LNPs. Among them, the flow rate ratio (FRR) and the total flow rate (TFR) have been shown to significantly influence the physicochemical characteristics of the produced particles. In particular, increasing the TFR or increasing the FRR decreased the particle size. The amino lipid choice (cationic—DOTAP and DDAB; ionisable—MC3), buffer choice (citrate buffer pH 6 or TRIS pH 7.4) and type of nucleic acid payload (PolyA, ssDNA or mRNA) have also been shown to have an impact on the characteristics of these LNPs. LNPs were shown to have a high (>90%) loading in all cases and were below 100 nm with a low polydispersity index (≤0.25). The results within this paper could be used as a guide for the development and scalable manufacture of LNP systems using microfluidics.
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spelling pubmed-76976822020-11-29 Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics Roces, Carla B. Lou, Gustavo Jain, Nikita Abraham, Suraj Thomas, Anitha Halbert, Gavin W. Perrie, Yvonne Pharmaceutics Article In the recent of years, the use of lipid nanoparticles (LNPs) for RNA delivery has gained considerable attention, with a large number in the clinical pipeline as vaccine candidates or to treat a wide range of diseases. Microfluidics offers considerable advantages for their manufacture due to its scalability, reproducibility and fast preparation. Thus, in this study, we have evaluated operating and formulation parameters to be considered when developing LNPs. Among them, the flow rate ratio (FRR) and the total flow rate (TFR) have been shown to significantly influence the physicochemical characteristics of the produced particles. In particular, increasing the TFR or increasing the FRR decreased the particle size. The amino lipid choice (cationic—DOTAP and DDAB; ionisable—MC3), buffer choice (citrate buffer pH 6 or TRIS pH 7.4) and type of nucleic acid payload (PolyA, ssDNA or mRNA) have also been shown to have an impact on the characteristics of these LNPs. LNPs were shown to have a high (>90%) loading in all cases and were below 100 nm with a low polydispersity index (≤0.25). The results within this paper could be used as a guide for the development and scalable manufacture of LNP systems using microfluidics. MDPI 2020-11-15 /pmc/articles/PMC7697682/ /pubmed/33203082 http://dx.doi.org/10.3390/pharmaceutics12111095 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roces, Carla B.
Lou, Gustavo
Jain, Nikita
Abraham, Suraj
Thomas, Anitha
Halbert, Gavin W.
Perrie, Yvonne
Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics
title Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics
title_full Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics
title_fullStr Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics
title_full_unstemmed Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics
title_short Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics
title_sort manufacturing considerations for the development of lipid nanoparticles using microfluidics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697682/
https://www.ncbi.nlm.nih.gov/pubmed/33203082
http://dx.doi.org/10.3390/pharmaceutics12111095
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