Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
Pedersen, Jannik N.
Schwartz Jr., Simó
Pedersen, Jan Skov
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.
577 - Bioquímica. Biologia molecular. Biofísica
Is part of
Journal of Supercritical Fluids
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.
Grant agreement number
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/
Producció de Remugants
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- ARTICLES CIENTÍFICS 
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