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David Simmang, Sven Schnichels, Jan Willem De Vries, Jose Hurst, Karl Ulrich Bartz-Schmidt, Andreas Hermann, Martin Stephan Spitzer; Lipid DNA Nanoparticles as a new type of medication carrier platform for the treatment of retinal diseases. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5027.
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© ARVO (1962-2015); The Authors (2016-present)
Recently, successful drug delivery via novel lipid DNA-Nanoparticles (NPs) as eye drops to the corneal epithelium was shown (ARVO 2014). Here we tested distribution and delivery of this class of NPs into the back of the eye to treat retinal diseases. A successful delivery via these NPs would offer chances to reduce the concentration of the drugs or reduce the number of injections needed per year.
NPs toxicity was first tested in 3 different cell lines with MTS, Caspase 3/7 assay and crystal violet (CV) staining. Afterwards fluorescently labelled NPs were injected either into the vitreous body or into subscleral tissue of ex vivo pig eyes obtained from the local slaughterhouse. After 5, 15, 30, 60 minutes of incubation the eyes were embedded into Tissue Tek and frozen in liquid nitrogen. Subsequently, cryo sections of the eyes were prepared and counterstained with DAPI. Using fluorescence microscopy the NP-diffusion and binding to different structures/tissues (retina, sclera, choroidea and pigment epithelium) was investigated. Finally, the NPs were injected into the vitreous body or the subscleral tissue of living rats. At several time points after injection the same parameters were investigated (30 min, 2, 4, 24 h).
No toxicity was observed in the 3 cell lines investigated with any of the three assays. Intravitreal injections into the pig eyes showed good binding to retinal cells, pigment epithelium, choroidal and scleral tissue. Subscleral injections showed similar results with diffusion obviously starting from the sclera and choroid in contrast to intravitreal injections. The in vivo injections into the vitreous body of living rats showed that the NPs bind to most of the tissue in the eye instantly, with residence times lasting up to 24 h.
Our results proof good binding of the NPs to retinal, choroidal and scleral tissue as well as to pigment epithelium with both intravitreal and subscleral injections. Thus DNA-NPs might be a versatile tool to prolong the residence time of intraocularly injected drugs. Further investigations with medical drugs are necessary to confirm these results.
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