The barrier role of the vitreoretinal interface toward intravitreal injected proteins, viruses and siRNA nanoparticles: ex vivo bovine screening models and siRNA nanoparticle design.

An intravitreal injection is a way of delivering medications to the retina in the back of the eye.
Anti-VEGF medications, for example, are injected monthly into the vitreous cavity after which they
diffuse to the retina which is separated from the vitreous with a very thin but difficult to penetrate
inner limiting membrane (ILM). The vitreous (the transparent gel that fills the center of the eye)
and ILM are strong barriers to therapeutics and even more to nanoparticles (NPs), such as viruses
or non-viral NPs containing siRNA or other therapeutics. NPs have however great potential to treat
retinal diseases if their delivery can be optimized. As the barrier role of vitreous and ILM cannot be
directly studied in human beings, we prepared two ex vivo models to study these barriers in the
cow eye. In this project, we have two objectives. First, we will study the applicability of the in
house developed ex vivo eye models to determine the delivery barriers after IVT injection of
marketed anti-VEGF medication and ‘in the pipeline’ viruses, currently evaluated in clinical trials.
Second, we will evaluate whether or not pre-clinical siRNA loaded NPs can compete with the
viruses and anti-VEGF medication. Therefore we will prepare solid lipid nanocapsules (SLNs) of 25,
50, 75 and 100 nm in order to investigate precisely the barrier-role of the ILM. Next, we will
prepare narrow-sized siRNA-loaded SLNs that will be tested for biological activity, intravitreal
mobility and ILM penetration.