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L. Tang, H. Weng, J. Zhou, Z. Hu; Nanoparticles for Intravitreal Controlled Drug Delivery . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4276.
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Purpose: Due to the poor penetration of the drugs to the posterior segments of eye and the complications of repeat intravitreal injections, we have investigated the use of polymeric nanoparticles made of N-isopropyl-acrylamide (NIPA) as carrier for controlled drug delivery in vitreous. Methods: The size of NIPA nanoparticles tested in this study is around 100 nm diameters. To assess the controlled drug release property, nanoparticles were loaded with cibacron blue dye and the release rate of blue dye was measured both in vitro and in vivo. The diffusibility and biocompatibility of the nanoparticles are determined in vivo. In an animal implantation model, 1 µl of FITC-labeled NIPA was injected into intravitral space of Swiss Webster mice. Following implantation for different periods of time, mice were sacrificed and the eyes were recovered for analyses. To assess the nanoparticles migration and biocompatibility, the eyes were fixed for frozen sections and the slides were then subjected to H&E and immunohistochemical staining for inflammatory cells. Results: In vitro the NIPA nanoparticles had a burst release initially, followed by a sustained release; the cumulative release at time points of 1, 2 and 7 days were 64.1±1.9%, 74.1±1.4% and 89.8±1.3%, respectively. At day 7 after intravitreal injection, the level of intravitreal blue dye with NIPA nanoparticles is significantly higher (approximately 20X) than the control (blue dye with no NIPA nanoparticles). Our in vivo studies have revealed that the distribution of NIPA nanoparticles was almost exclusively resided in the intravitreal space. No significant penetration through the sclera, choroid and retina was found. Furthermore, the anterior chamber was clear and no nanoparticles could be found in aqueous humor. On the other hand, intravitreal injection of NIPA appears to be well toletated. Histological section shows normal anatomy of all tissues in the eyes and no sign of inflammatory reaction was observed following 7-day implantation. Conclusions: This investigation has uncovered that NIPA nanoparticles is potentially useful as a controlled drug delivery system for treating vitreoretinal diseases such as uveitis, proliferative vitreoretinopathy, and endophthalmitis.
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