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Changbum Sim, Ji Yeon Park, Ji Hyun Park, Hyekyoung Hong, Seong Joon Ahn, Se Joon Woo, Kyu Hyung Park, Hyuncheol Kim; Development and Evaluation of a polysiRNA delivery system to the retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4952.
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To develop an optimized nano-sized polysiRNA-based therapeutic agent delivery system to the sub-retinal space for the treatment of age-related macular degeneration.
A nano-sized polysiRNA delivery system was developed by being coated with branched PEI and hyaluronic acid, step by step. The developed nano-sized delivery system was evaluated in vitro and in vivo. One day post the intravitreal injection into the mouse vitreous, the eye was enucleated to determine the distribution of nanoparticles in the retina. Anti-VEGF polysiRNA encapsulating nanoparticle was injected into the laser-photocoagulated eye intravitreally
All polysiRNA encapsulating nanoparicles showed a narrow size distribution (260.7 +/- 43.27 nm) and slightly negative charge (-4.98mV +/- 0.47 mV) because of the outermost hyaluronic acid layer. In vitro experiment, the nanoparticles were found to be up-taken into the RPE cells and inhibit the VEGF expression, compared to the control. The intravitreally injected nanoparticles overcame the vitreous barrier and reached the sub-retinal space. Anti-VEGF polysiRNA nanoparticle inhibited the choroidal neovascularization successfully. The polysiRNA nanoparticle showed no toxicity.
A polysiRNA encapsulating nanoparticles were developed by being coated with branched PEI and hyaluronic acid and found to deliver the siRNA-based therapeutic agent into the sub-retinal space successfully. The polysiRNA nanoparticles show great potential at the treatment of age-related macular degeneration.
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