Abstract
In her research, Naomi Teekamp investigated the stability and sustained release of protein-based drugs in formulations based on polymers. Proteins can be very potent drugs and have become indispensable in modern medicine, but their formulations can be drastically improved. In particular, proteins easily denature in aqueous injection solutions and the often-inevitable high frequency of injections is not patient-friendly. Although the latter aspect can be improved by the application of polymeric formulations for long-term release, the stability of proteins can still be an issue. By incorporating proteins in sugar glasses, they are shielded from harsh conditions during production of the formulation and are thereby stabilized. A novel combination of two sugars was evaluated in this thesis and some of the tested ratios were found to optimally stabilize proteins especially when exposed to high humidities.
Modification of proteins can further improve therapy, for example by enabling cell-specific delivery or targeting, which decreases side effects and increases efficacy. Different animal models were used in this thesis to show that the combination of polymer-based formulations and protein modification can result in sustained release of proteins that specifically accumulate in certain cells in fibrotic tissue.
This thesis offers some insights on how to achieve successful translation of promising, but often unstable, protein-based drugs to the clinic. Essential are performing formulation studies with the protein-based drug of interest instead of using model proteins. In addition, thorough characterization of these proteins, as well as clever choices for (polymeric) matrix materials and the production process of the formulation is warranted.
Modification of proteins can further improve therapy, for example by enabling cell-specific delivery or targeting, which decreases side effects and increases efficacy. Different animal models were used in this thesis to show that the combination of polymer-based formulations and protein modification can result in sustained release of proteins that specifically accumulate in certain cells in fibrotic tissue.
This thesis offers some insights on how to achieve successful translation of promising, but often unstable, protein-based drugs to the clinic. Essential are performing formulation studies with the protein-based drug of interest instead of using model proteins. In addition, thorough characterization of these proteins, as well as clever choices for (polymeric) matrix materials and the production process of the formulation is warranted.
Translated title of the contribution | Toediening van eiwitten vanuit polymere matrices: Van pre-formulering stabilisatiestudies tot locatiespecifieke toediening |
---|---|
Original language | English |
Qualification | Doctor of Philosophy |
Awarding Institution |
|
Supervisors/Advisors |
|
Award date | 20-Apr-2018 |
Place of Publication | [Groningen] |
Publisher | |
Print ISBNs | 978-94-6299-895-7 |
Electronic ISBNs | 978-94-6299-920-6 |
Publication status | Published - 2018 |