Delivery of biologicals: Sustained release of cell-specific proteins in fibrosis

van Dijk, F., 2018, [Groningen]: Rijksuniversiteit Groningen. 182 p.

Research output: ThesisThesis fully internal (DIV)

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  • Title and contents

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  • Chapter 1

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  • Chapter 2

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  • Chapter 3

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  • Chapter 4

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  • Chapter 5

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  • Chapter 6

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  • Chapter 7

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  • Chapter 8

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  • Complete thesis

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  • Propositions

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Chronic diseases are generally treated long-term with medication, associated with high patient-burden due to side effects and administration frequency. Fransien van Dijk’s research therefore focused on the development of a patient-friendly formulation for therapeutics for the chronic disease fibrosis. Fibrosis is hallmarked by the excessive deposition of scar tissue, ultimately replacing the functional cells. Myofibroblasts produce this scar tissue, and highly express the PDGFβ-receptor (PDGFβR). A promising strategy for a new, effective therapy with fewer side effects is the cell-specific delivery of drugs in myofibroblasts via the PDGFβR, by coupling of the drug to a PDGFβR-directed drug carrier. The first goal of her project was to evaluate all developed PDGFβR-directed protein constructs and obtain more insight in the mechanism of action of a potential antifibrotic drug (Fibroferon). Fransien van Dijk’s research showed that different therapeutically active proteins can be delivered in myofibroblasts via the PDGFβR. Another challenge in the application of therapeutic proteins is the administration route. Frequent intravenous injection are a high burden for patients. Therefore, Fransien van Dijk worked on polymeric microspheres that provide long-term and gradual release of a therapeutic protein. The second goal of her research was to develop a controlled release formulation for PDGFβR-directed constructs. Within 1 day after injection of the optimal formulation a constant drug concentration in blood was reached, which lasted long enough to exert an antifibrotic effect in the fibrotic organ. This brings the clinical application of a controlled release formulation for a cell-specific drug one step closer.
Translated title of the contributionAfgifte van biologische therapeutica: Het langdurig vrijgeven van celspecifieke eiwitten in fibrose
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Award date23-Mar-2018
Place of Publication[Groningen]
Print ISBNs978-94-034-0509-4
Electronic ISBNs978-94-034-0508-7
Publication statusPublished - 2018

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