Developing nanocapsules for the targeted drug delivery to the neuroretina

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Hereditary retinal degeneration (RD) is a group of rare retinopathies that cause progressive loss of vision. The degeneration and loss of photoreceptors in RD-type diseases is often associated with an excessive activation of cGMP-signalling. Previously, we highlighted the possibility to use inhibitory analogues of cGMP to reduce photoreceptor cell death in vitro and in vivo. The aim of the project is to deliver analogues of cGMP to the retina of RD animal models using a liposomal drug delivery system to reduce side effects and dosing frequency. The liposomes will need to facilitate the transport of the analogues through local, intravitreal injection, while offering protection from degradation of the analogues in the vitreous body and limiting the concentration of analogues needed to induce a positive effect in the retina. Simultaneously, the liposomes should also limit the dose frequency by providing a low drug release and less clearance from the vitreous body compared with free compound. The liposomes will be built from the bottom-up with design choices in mind (e.g. size, surface change, protein conjugation) that can potentially help meet these requirements. The project will address the biodistribution of different types of liposomes in the vitreous body, improve their targeting to photoreceptor cells by means of chemically attached molecular homing devices on the liposome surface, and screen for the mist suitable liposomal delivery system in terms of toxicity, photoreceptor protection, and preservation of retinal function.