Protein-Surfactant Interactions in Complex Systems : Study of Physical Stability of Proteins and Peptides
Protein-Tensid Interaktioner i Komplexa system : Studie av Protein and Peptiders Fysikaliska Stabilitet
Författare
Summary, in English
My objective has been to characterize protein-surfactant interactions in pharmaceutically relevant formulations. Thus, the behavior of selected excipients, proteins and peptides has been studied as the system in question is driven to the verge of instability in different manners; by inducing aggregation, by inducing surfactant complexation, or by inducing precipitation by increasing ionic strength in the presence of preservative. The system response is characterized, and concentration dependent transition points are identified, in the quest of elucidating molecular mechanisms. Two main themes emerge from this collected body of work.
Firstly, by building an understanding of the system at hand, starting with bench-top methods, and using that knowledge to design studies with more advanced methods like NMR, SANS or all atom molecular dynamics simulations, an integrative approach is established that can be applied to study physical stability and excipient interactions in formulation. In particular, the utility of NMR in characterizing the behavior of amphiphilic molecules, like surfactants, peptides or proteins, in complex systems is demonstrated.
Secondly, unexpected interactions between the protein human growth hormone (hGH) and the non-ionic surfactant dodecyl maltoside (DDM) are observed. No interaction or change in the protein conformation is observed in the presence of DDM alone. However, if an anionic surfactant like sodium dodecyl sulphate or a preservative like phenol is added, there are indications of hGH-DDM interactions. In summary, this goes to show that non-covalent interactions in pharmaceutical formulations are difficult to predict. Nonetheless, by applying the herein developed approach, the driving forces of the observed interactions can be identified.
Firstly, by building an understanding of the system at hand, starting with bench-top methods, and using that knowledge to design studies with more advanced methods like NMR, SANS or all atom molecular dynamics simulations, an integrative approach is established that can be applied to study physical stability and excipient interactions in formulation. In particular, the utility of NMR in characterizing the behavior of amphiphilic molecules, like surfactants, peptides or proteins, in complex systems is demonstrated.
Secondly, unexpected interactions between the protein human growth hormone (hGH) and the non-ionic surfactant dodecyl maltoside (DDM) are observed. No interaction or change in the protein conformation is observed in the presence of DDM alone. However, if an anionic surfactant like sodium dodecyl sulphate or a preservative like phenol is added, there are indications of hGH-DDM interactions. In summary, this goes to show that non-covalent interactions in pharmaceutical formulations are difficult to predict. Nonetheless, by applying the herein developed approach, the driving forces of the observed interactions can be identified.
Avdelning/ar
Publiceringsår
2024
Språk
Engelska
Fulltext
- Available as PDF - 10 MB
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Dokumenttyp
Doktorsavhandling
Förlag
Division of Food Technology, Lund University
Ämne
- Other Chemical Engineering
Nyckelord
- therapeutic proteins
- NMR (nuclear magnetic resonance)
- physical stability
- surfactant protein interaction
- preservative protein interaction
- peptide aggregation
Status
Published
Handledare
- Marie Wahlgren
- Lars Nilsson
- Adrian Sanchez-Fernandez
- Dan Lundberg
ISBN/ISSN/Övrigt
- ISBN: 978-91-8096-038-0
- ISBN: 978-91-8096-039-7
Försvarsdatum
23 maj 2024
Försvarstid
09:00
Försvarsplats
Lecture Hall KC:A, Kemicentrum, Sölvegatan 39, Faculty of Engineering LTH, Lund University, Lund. The dissertation will be live streamed, but part of the premises is to be excluded from the live stream.
Opponent
- Marco van de Weert (Prof.)