What you see is what you get: the physicochemistry of nanoparticles dictates how they cross ocular delivery barriers and alter autophagy

Promovendus/a
Karen Peynshaert
Faculteit
Faculteit Farmaceutische Wetenschappen
Vakgroep
Vakgroep Geneesmiddelenleer
Curriculum
Master in Drug Development, Ghent University, 2012 Bachelor in the Pharmaceutical Sciences, Ghent University, 2010
Academische graad
Doctor in de farmaceutische wetenschappen
Taal proefschrift
Engels
Vertaling titel
Wat je ziet is wat je krijgt: de fysicochemie van nanopartikels bepaalt hoe ze oculaire afleveringsbarrières overwinnen en autofagie beïnvloeden
Promotor(en)
Prof. dr., Katrien Remaut, UGent-Geneesmiddelenleer - Prof. dr. Stefaan De Smedt, UGent-Geneesmiddelenleer
Examencommissie
Prof. dr., Filip Van Nieuwerburgh, UGent-Geneesmiddelenleer - Prof. dr., Bruno De Geest, UGent-Geneesmiddelenleer - Prof. dr., Lieve Moons, KULeuven - Dr., Julie De Zaeytijd, UZ Gent - Prof. dr., Deniz Dalkara, Institut de la Vision - Prof. dr., François Paquet-Durand, University of Tübingen

Korte beschrijving

Vision impairment is estimated to affect 253 million people worldwide. This impairment can be provoked by a wide variety of retinal diseases for which several gene therapy strategies have been conceptualized. A primary requirement for these therapies, however, is the effective delivery of therapeutic genes to the retina which could be facilitated by packaging the genes in nanoparticles (NPs). Sadly, the delivery of therapeutic genes to the retina remains troublesome due to the many drug delivery barriers present at the back of the eye. Since the interaction of NPs with these drug delivery barriers remains poorly characterized the principal aim of this thesis was to gain insight into the various drug delivery barriers in the eye and more importantly, to explore the potential links between NP physicochemistry and the NPs’ ability to cross these barriers. Since we are convinced that intravitreal injection is a safe and straightforward ocular delivery method this thesis mainly focused on the vitreous and inner limiting membrane. We presented a novel ex vivo model that allows to investigate the interaction of NPs with the vitreoretinal interface which comprises the vitreous and the inner limiting membrane. Applying this model, we defined a size-dependent trend in the passage of NPs through the vitreoretinal interface and confirmed that the principal barrier to overcome for retinal entry is unquestionably the ILM. Based on our interest in applying Müller cells for the gene therapy strategy of ‘neuroprotection’, we also looked into the ability of Müller cells to take up a liposomal vector and process its nucleic acid cargo into protein. Finally, we explored the Müller cell’s performance in stressful circumstances by examining the liposome-induced transfection efficiency and cytotoxicity in hypoxic, hyperglycemic and oxidatively stressed cells – pathological conditions linked to diabetic retinopathy and glaucoma.

Praktisch

Wanneer
Dinsdag 10 april 2018, 18:00
Waar
Auditorium 1, Ottergemsesteenweg 460, 9000 Gent