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R. M. Dutescu, O. M. Merkel, L. Morawietz, T. Kissel, K. W. Ruether; Pegylated Polyethylenimin-Derivates (Peg-Pei), 2’O-Methyl-Modified-Sirna Co-Complexes as Non-Viral Vectors in Murine Ocular Tissue. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3121.
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The development of particle based carriers for antisense-strand nucleic acid drug delivery has become a major field of interest in ocular pharmaceutics. We investigated the suitability of pegylated polyethylenimine (PEG-PEI) derivates loaded with fluorescence labeled siRNA for non-viral delivery. Therefore, we analysed the ocular biodistribution and possible toxicity of PEG-PEI-derivates-siRNA complexes in mice.
Polyplexes of 2`O-methyl-modifiied fluorescence labelled siRNA and PEI/PEG-PEI derivates were synthesised. An N/P-ratio of 6 was chosen using PEI-, PEG-PEI-2K-, PEG-PEI-20k-2`O-methyl-siRNA complexes for intravitreal injection in 6 week old mice (female C57BL/6). After seven days rod and cone potentials were recorded by ganzfeld electroretinography. ERGs were performed in general anaesthesia before mice were sacrificed for histology. Retinal accumulation of complexes was shown in paraffin embedded sections by confocal microscopy.
PEG-PEI- o-methylated-siRNA- complexes show a pan-retinal enrichment in murine eyes. ERG recordings did not show any functional alterations in treated animals
The results suggest that PEG-PEI polymeres could be an adequate tool for retinal siRNA delivery
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