Aarhus University Seal / Aarhus Universitets segl

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Josep Merlo-Mas, NANOMOL TECHNOLOGIES SL
  • ,
  • Judit Tomsen-Melero, NANOMOL TECHNOLOGIES SL, CSIC - Institute of Materials Science of Barcelona, CIBER - Center for Biomedical Research Network
  • ,
  • José Luis Corchero, CIBER - Center for Biomedical Research Network, Autonomous University of Barcelona
  • ,
  • Elisabet González-Mira, CSIC - Institute of Materials Science of Barcelona, CIBER - Center for Biomedical Research Network
  • ,
  • Albert Font, Leanbio S.L
  • ,
  • Jannik N. Pedersen
  • ,
  • Natalia García-Aranda, CIBER - Center for Biomedical Research Network, Autonomous University of Barcelona
  • ,
  • Edgar Cristóbal-Lecina, CIBER - Center for Biomedical Research Network, CSIC - Institute for Advanced Chemistry of Catalonia
  • ,
  • Marta Alcaina-Hernando, NANOMOL TECHNOLOGIES SL
  • ,
  • Rosa Mendoza, CIBER - Center for Biomedical Research Network, Autonomous University of Barcelona
  • ,
  • Elena Garcia-Fruitós, CIBER - Center for Biomedical Research Network, Autonomous University of Barcelona
  • ,
  • Teresa Lizarraga, Leanbio S.L
  • ,
  • Susanne Resch, BIONANONET FORSCHUNGSGESELLSCHAFT MBH
  • ,
  • Christa Schimpel, BIONANONET FORSCHUNGSGESELLSCHAFT MBH
  • ,
  • Andreas Falk, BIONANONET FORSCHUNGSGESELLSCHAFT MBH
  • ,
  • Daniel Pulido, CIBER - Center for Biomedical Research Network, CSIC - Institute for Advanced Chemistry of Catalonia
  • ,
  • Miriam Royo, CIBER - Center for Biomedical Research Network, CSIC - Institute for Advanced Chemistry of Catalonia
  • ,
  • Simó Schwartz, CIBER - Center for Biomedical Research Network, Autonomous University of Barcelona
  • ,
  • Ibane Abasolo, CIBER - Center for Biomedical Research Network, Autonomous University of Barcelona
  • ,
  • Jan Skov Pedersen
  • Dganit Danino, Technion-Israel Institute of Technology
  • ,
  • Andreu Soldevila, Leanbio S.L
  • ,
  • Jaume Veciana, CSIC - Institute of Materials Science of Barcelona, CIBER - Center for Biomedical Research Network
  • ,
  • Santi Sala, NANOMOL TECHNOLOGIES SL
  • ,
  • Nora Ventosa, CSIC - Institute of Materials Science of Barcelona, CIBER - Center for Biomedical Research Network
  • ,
  • Alba Córdoba, NANOMOL TECHNOLOGIES SL

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 languageEnglish
Article number105204
JournalJournal of Supercritical Fluids
Volume173
Number of pages15
ISSN0896-8446
DOIs
Publication statusPublished - Jul 2021

Bibliographical note

Publisher Copyright:
© 2021

    Research areas

  • DELOS, Fabry disease, Protein-loaded liposomes, Quality by Design, Scale-up, α-galactosidase, NANOVESICLES, ?-galactosidase

See relations at Aarhus University Citationformats

ID: 219753565