April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Pegylated Polyethylenimin-Derivates (Peg-Pei), 2’O-Methyl-Modified-Sirna Co-Complexes as Non-Viral Vectors in Murine Ocular Tissue
R. M. Dutescu; O. M. Merkel; L. Morawietz; T. Kissel; K. W. Ruether
Author Affiliations & Notes
  • R. M. Dutescu
    Depatment of Ophthalmology (CVK),
    Charite, Berlin, Germany
  • O. M. Merkel
    Philipps-Universität, Institute for Pharmaceutical Technology and Biopharmacy, Marburg, Germany
  • L. Morawietz
    Pathology (CMK),
    Charite, Berlin, Germany
  • T. Kissel
    Pathology (CMK),
    Charite, Berlin, Germany
    Philipps-Universität, Institute for Pharmaceutical Technology and Biopharmacy, Marburg, Germany
  • K. W. Ruether
    Depatment of Ophthalmology (CVK),
    Charite, Berlin, Germany
    Philipps-Universität, Institute for Pharmaceutical Technology and Biopharmacy, Marburg, Germany
  • Footnotes
    Commercial Relationships  R.M. Dutescu, None; O.M. Merkel, None; L. Morawietz, None; T. Kissel, None; K.W. Ruether, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3121. doi:
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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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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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

Conclusions: : The results suggest that PEG-PEI polymeres could be an adequate tool for retinal siRNA delivery

Keywords: retina • gene transfer/gene therapy • vitreous substitutes 
© 2010, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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