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| Home > Articles > Published articles > Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method |
| Home > Articles > Published articles > Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method |
(Institut de Ciència de Materials de Barcelona) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut de Química Avançada de Catalunya) (Institut de Química Avançada de Catalunya) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Institut de Ciència de Materials de Barcelona) (Institut de Ciència de Materials de Barcelona)| Date: | 2021 |
| 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. |
| Grants: | European Commission 720942 Ministerio de Ciencia e Innovación CEX2019-000917-S Ministerio de Ciencia e Innovación PID2019-105622RB-1085 I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1439 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-918 Agència de Gestió d'Ajuts Universitaris i de Recerca SLT006/17/270 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Quality by Design ; DELOS ; Scale-up ; Protein-loaded liposomes ; Fabry disease ; α-galactosidase |
| Published in: | The Journal of Supercritical Fluids, Vol. 173 (July 2021) , art. 105204, ISSN 0896-8446 |
