Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations
Therapeutic proteins have great potentialities for the care of a wide spectrum of diseases, for which other small synthetic drugs result ineffective. Due to challenges related to their immunogenicity, the journey of biologics into clinics still faces obstacles. Among the causes of protein immunogeni...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Current Research in Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590262825000024 |
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| author | O. Bortone S. Fiorenza M. Baldassarre N. Falco M. Amidi T. Markkula P.A. Netti E. Torino |
| author_facet | O. Bortone S. Fiorenza M. Baldassarre N. Falco M. Amidi T. Markkula P.A. Netti E. Torino |
| author_sort | O. Bortone |
| collection | DOAJ |
| description | Therapeutic proteins have great potentialities for the care of a wide spectrum of diseases, for which other small synthetic drugs result ineffective. Due to challenges related to their immunogenicity, the journey of biologics into clinics still faces obstacles. Among the causes of protein immunogenicity, their natural propensity to aggregation is crucial, indeed, to study their stability, pharmaceutical formulations are generally exposed to diverse environmental physicochemical conditions. Traditional approaches to explore protein behavior are effort-demanding, lengthy and expensive, resulting in a limited knowledge of biomolecule stability. There is an urgent need to develop faster and more cost-effective technologies for biological formulation development. In this work, the conceptualization, design and implementation of a modular and automated microfluidic platform to provide thermal stress to highly concentrated and viscous pharmaceutical formulations is presented. The microfluidic platform validity in terms of reliability and comparability to a forced degradation batch-wise stimulation is demonstrated by thermally stimulating and analyzing through SE-HPLC (Size Exclusion – High Performance Liquid Chromatography) different high concentration (> 100 mg/ml) therapeutic nanobody-based formulations. Remarkably, the ranking of the formulations returned by the microfluidic thermal stress platform follows the same trend obtained through well-established industrial in-batch stimulations. Furthermore, data coming from microfluidic stimulations well correlates to outcomes coming from industrial methodologies for storage and accelerated stability studies. |
| format | Article |
| id | doaj-art-8831dcb9a0524e1b9045ce73335f050f |
| institution | Kabale University |
| issn | 2590-2628 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Biotechnology |
| spelling | doaj-art-8831dcb9a0524e1b9045ce73335f050f2025-01-26T05:04:50ZengElsevierCurrent Research in Biotechnology2590-26282025-01-019100273Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulationsO. Bortone0S. Fiorenza1M. Baldassarre2N. Falco3M. Amidi4T. Markkula5P.A. Netti6E. Torino7Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Italy; Global Drug Product Development, Merck Serono S.A., SwitzerlandDepartment of Information Technology and Electrical Engineering, University of Naples Federico II, ItalyGlobal Drug Product Development, Merck Serono S.A., SwitzerlandGlobal Drug Product Development, Merck Serono S.A., ItalyGlobal Drug Product Development, Merck Serono S.A., ItalyGlobal Drug Product Development, Merck Serono S.A., SwitzerlandDepartment of Chemical, Materials and Production Engineering, University of Naples Federico II, ItalyDepartment of Chemical, Materials and Production Engineering, University of Naples Federico II, Italy; Corresponding author at: Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Napoli 80125, Italy.Therapeutic proteins have great potentialities for the care of a wide spectrum of diseases, for which other small synthetic drugs result ineffective. Due to challenges related to their immunogenicity, the journey of biologics into clinics still faces obstacles. Among the causes of protein immunogenicity, their natural propensity to aggregation is crucial, indeed, to study their stability, pharmaceutical formulations are generally exposed to diverse environmental physicochemical conditions. Traditional approaches to explore protein behavior are effort-demanding, lengthy and expensive, resulting in a limited knowledge of biomolecule stability. There is an urgent need to develop faster and more cost-effective technologies for biological formulation development. In this work, the conceptualization, design and implementation of a modular and automated microfluidic platform to provide thermal stress to highly concentrated and viscous pharmaceutical formulations is presented. The microfluidic platform validity in terms of reliability and comparability to a forced degradation batch-wise stimulation is demonstrated by thermally stimulating and analyzing through SE-HPLC (Size Exclusion – High Performance Liquid Chromatography) different high concentration (> 100 mg/ml) therapeutic nanobody-based formulations. Remarkably, the ranking of the formulations returned by the microfluidic thermal stress platform follows the same trend obtained through well-established industrial in-batch stimulations. Furthermore, data coming from microfluidic stimulations well correlates to outcomes coming from industrial methodologies for storage and accelerated stability studies.http://www.sciencedirect.com/science/article/pii/S2590262825000024High concentration biologicsProtein aggregationMiniaturizationAutomated microfluidicsMicrofabricationProcess control |
| spellingShingle | O. Bortone S. Fiorenza M. Baldassarre N. Falco M. Amidi T. Markkula P.A. Netti E. Torino Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations Current Research in Biotechnology High concentration biologics Protein aggregation Miniaturization Automated microfluidics Microfabrication Process control |
| title | Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations |
| title_full | Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations |
| title_fullStr | Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations |
| title_full_unstemmed | Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations |
| title_short | Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations |
| title_sort | design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations |
| topic | High concentration biologics Protein aggregation Miniaturization Automated microfluidics Microfabrication Process control |
| url | http://www.sciencedirect.com/science/article/pii/S2590262825000024 |
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