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Sven Schnichels, David Simmang, Lisa Strudel, Jose Hurst, Jan Willem de Vries, Karl Ulrich Bartz-Schmidt, Andreas Herrmann, Martin Stephan Spitzer; DNA Nanoparticles for the Treatment of Retinal Diseases: in-vivo results. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5683.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal diseases (AMD, DME, etc) in regard to ocular drug delivery are difficult to treat and therefore therapy is associated with numerous side effects. Currently, intravitreal injections or topical drug application result in only a limited duration time of the active agent in the eye and consequently lack efficiency. Therefore, a novel method of drug delivery is desirable in order to enhance the performance of the treatments and reduce side effects as much as possible. At the ARVO 2015 we presented promising ex-vivo and first in-vivo results with our drug delivery system based on DNA-NPs for the treatment of retinal diseases. In particular two variations of the DNA-NPs displayed superior characteristics in the ex-vivo setup and were therefore employed in the here presented in-vivo investigations.
The half-life time and adhesion capacity of the NPs to specific ocular tissues was tested. Several DNA-NPs were designed to find the best structural properties of these NPs for improved adhesion capabilities. The fluorescently-labelled NPs were injected in rats and their diffusion and adherence was monitored by fluorescence photometry and microscopy. Finally, to explore the use of this platform for delivery using a periocular administration route, they were also employed in subconjunctival injections and the same parameters as described before were investigated.
Efficient retention in the vitreous body was evident up to 3 days and the presence of the NPs could be confirmed up to 5 days in in-vivo experiments. As an example, after day one 4/6 eyes were still positive for one of the NPs. This effect decreased to 3/6 eyes 3 days post injection. To explore the use of alternative application routes, the NPs were also applied via subconjunctival injections. Here the results indicate even more promising properties. The NPs were notably accumulating on the scleral surface of the eyes. In detail, after 1 day of incubation the same NP was present on 5/6 eyes and even 6/6 eyes were detected with NPs in the subconjunctival tissue at 3 days post injection.
The use of our DNA-NPs could lead to sufficient intraocular drug concentration for several days, preventing unneeded intravitreal injections in future treatments. These promising results invite to conduct further research regarding the efficacy of delivered medication and establishing the DNA based NPs as drug delivery platform for the posterior segment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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