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T.W. Prow, S. Kim, I. Bhutto, R. Grebe, G.A. Lutty; In vivo Toxicity of Nanoparticle Delivered Genes . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1790.
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These studies were designed to evaluate several nanoparticle–based gene delivery tools in vivo. Chitosan (CHI), biodegradable polyphosphoester (PCEP), and magnetic (MNP) nanoparticles were successful gene delivery tools in vitro. We have characterized the toxicities of these three nanoparticles in the rabbit eye.
Two month–old rabbits were injected with nanoparticles by intravitreal (IV) or sub–retinal (SR) routes and maintained for 7 days after injection. At sacrifice, the eyes were enucleated, dissected and evaluated for: vitreous clarity, retinal anomalies (degeneration, thickening, traction, and folding), fibrosis, RPE abnormalities, and inflammation. Chitosan, PCEP, and MNP were made as described in Leong et al (1998), Wen et al (2004), and Prow et al (2006). All eyes were cryopreserved after examination and later sectioned for further analysis. A total of 14 eyes were injected with vehicle, 47 eyes with DNA alone, 15 eyes with CHI, 31 eyes with PCEP, and 21 eyes with MNP.
Each of the nanoparticles tested were non–toxic in vitro but showed varying levels of toxicity in vivo. All of the nanoparticles were able to transfect cells in vitro and in vivo. The vehicle and DNA alone injected eyes showed low to no levels of toxicity. Chitosan, on the other hand, showed inflammation in 92% of eyes (12/13). These nanoparticles also caused membranous opacity (62%, 8/13) and hazy vitreous in 38% or 5/13 eyes. Neither PCEP nor MNP IV injection led to inflammation nor induced retinal dysfunction. In PCEP and MNP SR eyes, MNP were the least toxic. PCEP injected SR induced RPE abnormalities in 11% (3/27) and retinal degeneration in 15% (4/27).
Most investigators place enormous emphasis on the transfection efficiency of nanoparticles in vitro. However, from our experience, the most successful nanoparticle in vitro was CHI, but, unfortunately, it was also the most toxic in vivo. Therefore, we conclude that the least toxic nanoparticle tested, MNP, is the best nanoparticle for in vivo studies of those tested.
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