ALL libraries (COBIB.SI union bibliographic/catalogue database)
13.
Vpliv kakovosti polisorbata 80 na fizikalno stabilnost monoklonskega protitelesa = The impact of polysorbate 80 quality on the physical stability of a monoclonal antibody ; enoviti magistrski študijski program Farmacija
Božič, Ula
Complex three-dimensional structure of therapeutic proteins and their tendency for aggregate formation, is a challenge for biopharmaceutical companies, since such aggregates can evoke an immune ...response upon administration, cause blood vessel occlusion and lead to loss of effective monomeric proteins. Polysorbates (PS) are surface active ingredients, which are commonly supplemented to biopharmaceutical formulations with intention of preventing aggregation. They are heterogenous mixtures of a PEGylated sorbitan core with one or multiple esterified fatty acids. Although PS molecular mechanism of action is well investigated, it is to this date still not clear how different quality grades compare in stabilizing proteins. Moreover, impact of (partly) degraded PS on protein stability is not fully understood. In this thesis, a monoclonal antibody (IgG) was subjected to pumping, stirring and dropping stress, which mimic applied mechanical stresses to a proteinaceous drug product during manufacturing, transportation and administration. Protein was formulated with two PS 80 quality grades, one compliant with Ph.Eur., USP and JP, and the other in line with stricter ChP. Furthermore, the antibody was supplemented with (partly) hydrolyzed PS 80. LC-CAD was performed to confirm successful degradation and to assess PS 80 concentrations used in this study. Surfactant functionality was assessed by measuring the extent of protein aggregation. Particles in nano- and micro-meter size range were characterized by using particle characterization techniques, such as micro-flow imaging (MFI), backgrounded membrane imaging (BMI) and dynamic light scattering (DLS). Additionally, turbidity and soluble protein aggregates were analyzed by using UV spectroscopy and ultra-high performance size exclusion chromatography (UP-SEC), respectively. We noticed a concentration range, where PS 80 is effective. No discrepancy in functionality was observed for two quality grades. Fully degraded PS 80 does not possess any stabilizing properties. When a portion (more than ~10 %) of neat PS is degraded, this results in poorer protection of the antibody under mechanical stress. Similarly, presence of extra degradants at the same intact PS 80 concentration was found to be destabilizing. More studies should be carried out with focus on development of repeatable stress methods and examination of oxidized PS functionality.
Type of material - master's thesis
; adult, serious
Publication and manufacture - Ljubljana : [U. Božič], 2019
It was not necessary to add the material to the shelf.
Bibliographic material was successfully added on shelf.
Adding bibliographical material on shelf was not successful.
Material is already on the shelf.
Permalink
URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year
Impact factor
Edition
Category
Classification
JCR
SNIP
JCR
SNIP
JCR
SNIP
JCR
SNIP
Select the library membership card:
DRS,
in which the journal is indexed
Database name
Field
Year
Links to authors' personal bibliographies
Links to information on researchers in the SICRIS system
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
