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Title:          Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
Subject:        The Journal of Supercritical Fluids, 173 (2021) 105204. doi:10.1016/j.supflu.2021.105204
Keywords:       Quality by Design; DELOS; Scale-up; Protein-loaded liposomes; Fabry disease; α-galactosidase; 
Author:         Josep Merlo-Mas
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     Item: 
      Title: Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
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        Title: 1 Introduction
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        Title: 2 Materials and methods
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          Title: 2.1 Materials
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          Title: 2.2 Methods
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           Item: 
            Title: 2.2.1 NanoGLA preparation
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           Item: 
            Title: 2.2.2 Separation of the free GLA from the nanoGLA liposomal dispersion by diafiltration and concentration process
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            Title: 2.2.3 Characterization of liposomes
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            Title: 2.2.3.1 Mean particle size, PdI and ζ-potential
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            Title: 2.2.3.2 Turbiscan Stability Index
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            Title: 2.2.3.3 Morphology
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            Title: 2.2.3.4 Uni-lamellarity
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            Title: 2.2.3.5 Entrapment efficiency
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            Title: 2.2.3.6 Enzymatic activity
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            Title: 2.2.4 Experimental design and data processing
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        Title: 3 Results and discussion
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          Title: 3.1 Identification of the Critical Quality Attributes (CQAs)
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          Title: 3.2 Risk assessment and control strategies
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          Title: 3.3 Experimental design and development
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         Item: 
          Title: 3.4 Characterization of the intermediate nanoGLA obtained
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         Item: 
          Title: 3.5 Analysis of the influence of the factors on CQAs
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         Item: 
          Title: 3.6 Evaluation of the design space
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          Title: 3.7 Optimization of the nanoGLA formulation
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          Title: 3.8 Safe-by-Design implementation
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        Title: 4 Conclusions
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       Item: 
        Title: Declaration of Competing Interest
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       Item: 
        Title: Acknowledgments
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       Item: 
        Title: Appendix A Synthesis of GLAcmycHis
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          Title: Plasmids and E. coli strains
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          Title: Mammalian cell line, transfection and selection of positive clones
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         Item: 
          Title: Cryopreservation of CHO-DG44-GLA clone #3
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         Item: 
          Title: Production and purification of extracellular GLAcmycHis protein
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        Title: Appendix B DELOS-susp methodology for the preparation of nanoGLA
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        Title: Appendix C Risk analysis assessment
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        Title: Appendix D Samples time evolution of mean particle size, PdI, and ζ-potential
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        Title: Appendix E Modeling and data fitting
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        Title: Appendix F Identified safety issues
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        Title: References
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