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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Aggregation mechanisms of proteins in liquid formulations / Aggregationsmekanismer av proteiner i vätskeformuleringar

Hamrin, Amanda January 2022 (has links)
Biologiska läkemedel har under det senaste århundradet utökats, och under de senaste 25 åren så har proportionen av godkända biologiska läkemedel har ökat för behandlingen av sjukdomar, vaccin, och diagnostik. Det finns flera olika mekanismer för protein aggregering, och en av dessa är seeding, vilket innebär aggregering inducerat av tillsatta aggregat eller förekomsten av strukturförändringar i proteinet. I detta examensarbete har två terapeutiska proteiner, Somatropin och en monoklonal antikropp, studerats i form av aggregering. Denna studie har utförts genom att värma en del av proteinlösningen för att bilda aggregat och strukturförändrat protein, och sedan blanda detta med nativt protein till olika volymprocent. Dessa lösningar förvarades i olika temperaturer, 4°C, RT och 40°C för att undersöka temperaturberoendet. Med Dynamic Light Scattering (DLS) mättes storleksfördelningen och medelstorleken på proteinet, vilket visade att de seedade proverna ökade i medelstorlek med tiden. Detta indikerar att seedingen inducerade aggregering med tiden. / Biological pharmaceuticals have expanded their use over the last decade, and during the recent 25 years, the proportion of approved biologics has increased for the treatment of diseases, vaccines, and diagnostics. There are several aggregation mechanisms, and one is seeding, i.e., aggregation induced by pre-formed aggregates or the presence of conformational changed proteins. In this master thesis, two therapeutic proteins, Somatropin and one monoclonal antibody have been studied in terms of aggregation. The study has been performed by heating a part of a protein solution to induce aggregation and mixing this with native protein in different volume percentages. These were stored in different temperatures, 4°C, RT, and 40°C, to investigate the temperature dependence. With Dynamic light scattering (DLS), the size distribution and the average-sized particles were measured. This showed that there was a growth of average size in the seeded samples with time. This indicates that the seeding induced aggregation with time.

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