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Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method

Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fi...

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Autores principales: Merlo-Mas, Josep, Tomsen-Melero, Judit, Corchero, José-Luis, González-Mira, Elisabet, Font, Albert, Pedersen, Jannik N., García-Aranda, Natalia, Cristóbal-Lecina, Edgar, Alcaina-Hernando, Marta, Mendoza, Rosa, Garcia-Fruitós, Elena, Lizarraga, Teresa, Resch, Susanne, Schimpel, Christa, Falk, Andreas, Pulido, Daniel, Royo, Miriam, Schwartz, Simó, Abasolo, Ibane, Pedersen, Jan Skov, Danino, Dganit, Soldevila, Andreu, Veciana, Jaume, Sala, Santi, Ventosa, Nora, Córdoba, Alba
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PRA Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085735/
https://www.ncbi.nlm.nih.gov/pubmed/34219919
http://dx.doi.org/10.1016/j.supflu.2021.105204
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author Merlo-Mas, Josep
Tomsen-Melero, Judit
Corchero, José-Luis
González-Mira, Elisabet
Font, Albert
Pedersen, Jannik N.
García-Aranda, Natalia
Cristóbal-Lecina, Edgar
Alcaina-Hernando, Marta
Mendoza, Rosa
Garcia-Fruitós, Elena
Lizarraga, Teresa
Resch, Susanne
Schimpel, Christa
Falk, Andreas
Pulido, Daniel
Royo, Miriam
Schwartz, Simó
Abasolo, Ibane
Pedersen, Jan Skov
Danino, Dganit
Soldevila, Andreu
Veciana, Jaume
Sala, Santi
Ventosa, Nora
Córdoba, Alba
author_facet Merlo-Mas, Josep
Tomsen-Melero, Judit
Corchero, José-Luis
González-Mira, Elisabet
Font, Albert
Pedersen, Jannik N.
García-Aranda, Natalia
Cristóbal-Lecina, Edgar
Alcaina-Hernando, Marta
Mendoza, Rosa
Garcia-Fruitós, Elena
Lizarraga, Teresa
Resch, Susanne
Schimpel, Christa
Falk, Andreas
Pulido, Daniel
Royo, Miriam
Schwartz, Simó
Abasolo, Ibane
Pedersen, Jan Skov
Danino, Dganit
Soldevila, Andreu
Veciana, Jaume
Sala, Santi
Ventosa, Nora
Córdoba, Alba
author_sort Merlo-Mas, Josep
collection PubMed
description Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients. In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability. Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease. Through a risk analysis and a Design of Experiments (DoE), we obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing.
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spelling pubmed-80857352021-07-01 Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method Merlo-Mas, Josep Tomsen-Melero, Judit Corchero, José-Luis González-Mira, Elisabet Font, Albert Pedersen, Jannik N. García-Aranda, Natalia Cristóbal-Lecina, Edgar Alcaina-Hernando, Marta Mendoza, Rosa Garcia-Fruitós, Elena Lizarraga, Teresa Resch, Susanne Schimpel, Christa Falk, Andreas Pulido, Daniel Royo, Miriam Schwartz, Simó Abasolo, Ibane Pedersen, Jan Skov Danino, Dganit Soldevila, Andreu Veciana, Jaume Sala, Santi Ventosa, Nora Córdoba, Alba J Supercrit Fluids Article Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients. In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability. Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease. Through a risk analysis and a Design of Experiments (DoE), we obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing. PRA Press 2021-07 /pmc/articles/PMC8085735/ /pubmed/34219919 http://dx.doi.org/10.1016/j.supflu.2021.105204 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Merlo-Mas, Josep
Tomsen-Melero, Judit
Corchero, José-Luis
González-Mira, Elisabet
Font, Albert
Pedersen, Jannik N.
García-Aranda, Natalia
Cristóbal-Lecina, Edgar
Alcaina-Hernando, Marta
Mendoza, Rosa
Garcia-Fruitós, Elena
Lizarraga, Teresa
Resch, Susanne
Schimpel, Christa
Falk, Andreas
Pulido, Daniel
Royo, Miriam
Schwartz, Simó
Abasolo, Ibane
Pedersen, Jan Skov
Danino, Dganit
Soldevila, Andreu
Veciana, Jaume
Sala, Santi
Ventosa, Nora
Córdoba, Alba
Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
title Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
title_full Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
title_fullStr Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
title_full_unstemmed Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
title_short Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
title_sort application of quality by design to the robust preparation of a liposomal gla formulation by delos-susp method
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085735/
https://www.ncbi.nlm.nih.gov/pubmed/34219919
http://dx.doi.org/10.1016/j.supflu.2021.105204
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