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

Josep Merlo-Mas; Judit Tomsen-Melero; José Luis Corchero; Elisabet González-Mira; Albert Font; Jannik N. Pedersen; Natalia García-Aranda; Edgar Cristóbal-Lecina; Marta Alcaina-Hernando; Rosa Mendoza; Elena Garcia-Fruitós; Teresa Lizarraga; Susanne Resch; Christa Schimpel; Andreas Falk; Daniel Pulido; Miriam Royo; Simó Schwartz; Ibane Abasolo; Jan Skov Pedersen; Dganit Danino; Andreu Soldevila; Jaume Veciana; Santi Sala; Nora Ventosa; Alba Córdoba

doi:10.1016/j.supflu.2021.105204

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

Josep Merlo-Mas, Judit Tomsen-Melero, José Luis Corchero, Elisabet González-Mira, Albert Font, Jannik N. Pedersen, Natalia García-Aranda, Edgar Cristóbal-Lecina, Marta Alcaina-Hernando, Rosa Mendoza, Elena Garcia-Fruitós, Teresa Lizarraga, Susanne Resch, Christa Schimpel, Andreas Falk, Daniel Pulido, Miriam Royo, Simó Schwartz, Ibane Abasolo, Jan Skov PedersenDganit Danino, Andreu Soldevila, Jaume Veciana, Santi Sala, Nora Ventosa^*, Alba Córdoba^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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.

Original language	English
Article number	105204
Journal	Journal of Supercritical Fluids
Volume	173
DOIs	https://doi.org/10.1016/j.supflu.2021.105204
State	Published - Jul 2021
Externally published	Yes

Keywords

DELOS
Fabry disease
Protein-loaded liposomes
Quality by Design
Scale-up
α-galactosidase

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10.1016/j.supflu.2021.105204

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Merlo-Mas, J., Tomsen-Melero, J., Corchero, J. L., González-Mira, E., Font, A., Pedersen, J. N., García-Aranda, N., Cristóbal-Lecina, E., Alcaina-Hernando, M., Mendoza, R., Garcia-Fruitós, E., Lizarraga, T., Resch, S., Schimpel, C., Falk, A., Pulido, D., Royo, M., Schwartz, S., Abasolo, I., ... Córdoba, A. (2021). Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method. Journal of Supercritical Fluids, 173, Article 105204. https://doi.org/10.1016/j.supflu.2021.105204

@article{324457b6d9de4d3d827d36377c12475d,

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

abstract = "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.",

keywords = "DELOS, Fabry disease, Protein-loaded liposomes, Quality by Design, Scale-up, α-galactosidase",

author = "Josep Merlo-Mas and Judit Tomsen-Melero and Corchero, {Jos{\'e} Luis} and Elisabet Gonz{\'a}lez-Mira and Albert Font and Pedersen, {Jannik N.} and Natalia Garc{\'i}a-Aranda and Edgar Crist{\'o}bal-Lecina and Marta Alcaina-Hernando and Rosa Mendoza and Elena Garcia-Fruit{\'o}s and Teresa Lizarraga and Susanne Resch and Christa Schimpel and Andreas Falk and Daniel Pulido and Miriam Royo and Sim{\'o} Schwartz and Ibane Abasolo and Pedersen, {Jan Skov} and Dganit Danino and Andreu Soldevila and Jaume Veciana and Santi Sala and Nora Ventosa and Alba C{\'o}rdoba",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = jul,

doi = "10.1016/j.supflu.2021.105204",

language = "英语",

volume = "173",

journal = "Journal of Supercritical Fluids",

issn = "0896-8446",

publisher = "Elsevier",

}

Merlo-Mas, J, Tomsen-Melero, J, Corchero, JL, González-Mira, E, Font, A, Pedersen, JN, García-Aranda, N, Cristóbal-Lecina, E, Alcaina-Hernando, M, Mendoza, R, Garcia-Fruitós, E, Lizarraga, T, Resch, S, Schimpel, C, Falk, A, Pulido, D, Royo, M, Schwartz, S, Abasolo, I, Pedersen, JS, Danino, D, Soldevila, A, Veciana, J, Sala, S, Ventosa, N & Córdoba, A 2021, 'Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method', Journal of Supercritical Fluids, vol. 173, 105204. https://doi.org/10.1016/j.supflu.2021.105204

TY - JOUR

T1 - Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method

AU - Merlo-Mas, Josep

AU - Tomsen-Melero, Judit

AU - Corchero, José Luis

AU - González-Mira, Elisabet

AU - Font, Albert

AU - Pedersen, Jannik N.

AU - García-Aranda, Natalia

AU - Cristóbal-Lecina, Edgar

AU - Alcaina-Hernando, Marta

AU - Mendoza, Rosa

AU - Garcia-Fruitós, Elena

AU - Lizarraga, Teresa

AU - Resch, Susanne

AU - Schimpel, Christa

AU - Falk, Andreas

AU - Pulido, Daniel

AU - Royo, Miriam

AU - Schwartz, Simó

AU - Abasolo, Ibane

AU - Pedersen, Jan Skov

AU - Danino, Dganit

AU - Soldevila, Andreu

AU - Veciana, Jaume

AU - Sala, Santi

AU - Ventosa, Nora

AU - Córdoba, Alba

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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.

KW - DELOS

KW - Fabry disease

KW - Protein-loaded liposomes

KW - Quality by Design

KW - Scale-up

KW - α-galactosidase

UR - http://www.scopus.com/inward/record.url?scp=85102894750&partnerID=8YFLogxK

U2 - 10.1016/j.supflu.2021.105204

DO - 10.1016/j.supflu.2021.105204

M3 - 文章

AN - SCOPUS:85102894750

SN - 0896-8446

VL - 173

JO - Journal of Supercritical Fluids

JF - Journal of Supercritical Fluids

M1 - 105204

ER -

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

Abstract

Keywords

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