Protein-Surfactant Interactions in Complex Systems : Study of Physical Stability of Proteins and Peptides
(2024)- Abstract
- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/f9e24a66-c60c-437b-9e46-31769ee114fd
- author
- Hjalte, Johanna LU
- supervisor
- opponent
-
- Prof. van de Weert, Marco, University of Copenhagen, Denmark.
- organization
- alternative title
- Protein-Tensid Interaktioner i Komplexa system : Studie av Protein and Peptiders Fysikaliska Stabilitet
- publishing date
- 2024
- type
- Thesis
- publication status
- published
- subject
- keywords
- therapeutic proteins, NMR (nuclear magnetic resonance), physical stability, surfactant protein interaction, preservative protein interaction, peptide aggregation
- pages
- 242 pages
- publisher
- Division of Food Technology, Lund University
- defense location
- 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.
- defense date
- 2024-05-23 09:00:00
- ISBN
- 978-91-8096-039-7
- 978-91-8096-038-0
- language
- English
- LU publication?
- yes
- id
- f9e24a66-c60c-437b-9e46-31769ee114fd
- date added to LUP
- 2024-04-22 11:52:10
- date last changed
- 2024-04-25 08:27:34
@phdthesis{f9e24a66-c60c-437b-9e46-31769ee114fd,
abstract = {{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. <br/><br/>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. <br/><br/>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.}},
author = {{Hjalte, Johanna}},
isbn = {{978-91-8096-039-7}},
keywords = {{therapeutic proteins; NMR (nuclear magnetic resonance); physical stability; surfactant protein interaction; preservative protein interaction; peptide aggregation}},
language = {{eng}},
publisher = {{Division of Food Technology, Lund University}},
school = {{Lund University}},
title = {{Protein-Surfactant Interactions in Complex Systems : Study of Physical Stability of Proteins and Peptides}},
url = {{https://lup.lub.lu.se/search/files/181260392/Avhandling_Johanna_Hjalte_utan_papers_Lucris.pdf}},
year = {{2024}},
}