The blood-brain barrier (BBB) consists of brain endothelial cells that prevent the passage of potentially harmful compounds from the blood into the brain. As a consequence, the BBB greatly hampers the treatment of brain diseases by limiting the entry of therapeutics into the brain. The effective treatment of brain diseases is further precluded by the enzymatic degradation of therapeutic molecules in the blood. Applying polymersomes for the transport of a therapeutic agent across the BBB seems a promising strategy for its delivery to the brain. Drugs can be encapsulated in these spherical nanoparticles composed of polymers in order to protect the therapeutics from degradation during circulation in the blood. The surface of polymersomes can be decorated with a ligand that stimulates the uptake of the drug-loaded nanoparticle by brain endothelial cells. This thesis described the design of biodegradable polymersomes that were decorated with the G23 peptide, which is a ligand that was shown to promote the transport of different types of nanoparticles across the BBB. A filter-free BBB model was developed in order to demonstrate the distinctive capacity of the G23 peptide to transport the biodegradable polymersomes across the BBB. The results of this study suggest that G23 polymersomes have the potential to become nanocarriers that enable effective treatment of brain diseases.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2020|