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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PRA Press
2021
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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. |
format | Online Article Text |
id | pubmed-8085735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | PRA Press |
record_format | MEDLINE/PubMed |
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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