Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
Ver/Abrir
Autor/a
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
Lizarraga, Teresa
Resch, Susanne
Schimpel, Christa
Falk, Andreas
Pulido, Daniel
Royo, Miriam
Schwartz Jr., Simó
Abasolo, Ibane
Pedersen, Jan Skov
Danino, Dganit
Soldevila, Andreu
Veciana, Jaume
Sala, Santi
Ventosa, Nora
Córdoba, Alba
Fecha de publicación
2021-02-19ISSN
0896-8446
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
577 - Bioquímica. Biología molecular. Biofísica
Páginas
15
Publicado por
Elsevier
Publicado en
Journal of Supercritical Fluids
Citación
Merlo-Mas, Josep, Judit Tomsen-Melero, José-Luis Corchero, Elisabet González-Mira, Albert Font, Jannik N. Pedersen, and Natalia García-Aranda et al. 2021. "Application Of Quality By Design To The Robust Preparation Of A Liposomal GLA Formulation By DELOS-Susp Method". The Journal Of Supercritical Fluids 173: 105204. doi:10.1016/j.supflu.2021.105204.
Número del acuerdo de la subvención
EC/H2020/720942/EU/Smart multifunctional GLA-nanoformulation for Fabry disease/Smart-4-Fabry
MICIU-AEI/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-105622RB-I00/ES/PROCESAMIENTO DE MOLECULAS PARA CREAR MATERIALES HIBRIDOS ESTRUCTURADOS JERARQUICAMENTE PARA APLICACIONES BIOMEDICAS/
Program
Producció de Remugants
Este ítem aparece en la(s) siguiente(s) colección(ones)
- ARTICLES CIENTÍFICS [2811]
Excepto si se señala otra cosa, la licencia del ítem se describe como http://creativecommons.org/licenses/by/4.0/