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Hyuncheol Kim, Hyunkoo Han, Heebeom Koo, Jin H. Na, Kwangmeyung Kim; Development Of An Optimized Nano-sized Sirna Delivery System To The Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):428.
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To develop an optimized nano-sized siRNA-based therapeutic agent delivery system to the sub-retinal space for the treatment of age-related macular degeneration.
Three nano-sized delivery systems (self-assembled hyaluronic acid nanoparticle, glycosylated chitosan nanoparticle, albumin-based nanoparticle) were evaluated to determine which particle is the best for the delivery of siRNA-based nanoparticle to the sub-retinal space. One day post the intravitreal injection into the rat vitreous, the eye was enucleated to determine the distribution of nanoparticles in the retina. Anti-VEGF siRNA encapsulated albumin nanoparticle was injected into the later-photocoagulated eye intravitreally.
All nanoparticle showed a narrow size distribution, around 200 nm. Both hyaluronic acid nanoparticle and albumin nanoparticle show slightly negative; on the other hand, glycosylated chitosan nanoparticle shows positive charge. All of three nanoparticle could overcome the vitreous barrier and reach the retina. However, glycosylated nanoparticle could not penetrate the retina structure. The other two particles penetrated the retinal structure into the sub-retinal space successfully. Anti-VEGF siRNA encapsulated albumin nanoparticle inhibited the choroidal neovascularization successfully.
The penetration of intravitreal nanoparticles depended on the surface charge of a nanoparticle. The albumin-based nanoparticle was better for the siRNA delivery into the sub-retinal space than the glycosylated chitosan nanoparticle and self-assembled hyaluronic acid nanoparticle.
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