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L. Tang, Y.-T. Tsai, W. Hu; Three-dimensional Model for Quantifying Nanoparticle Drug Delivery in Eyes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5963.
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Nanoparticles have been used as carriers for targeted drug delivery. However, the efficiency of nanoparticle drug delivery is hard to assess using either histological evaluation or 3D imaging methods (MRI and CT). To solve such deficiency, a 3D drug distribution model has been developed to provide the visual and quantitative information for drug delivery in the eye.
Poly-N-isopropylamide (PNIPAM) nanoparticles (~100 nm diameter) labeled with fluorescein isothiocyanate (FITC) were used in this investigation. After injected intravitreally with FITC-PNIPAM (0.5µg/25µl) for 3 days, the eyes were recovered and frozen sectioned. The tissue sections were then scanned by a microarray scanner (Genepix 4000B). The fluorescence intensity was converted to particle concentrations.
The images using microarray scanner were very reproducible and consistent than those taken with fluorescence microscope. The scanner images had much higher resolution (20 X 20 µm) and sensitivity than CT and MRI (~400 X 400 µm). To build 3D eye model based on histological sections, a two-step process has been established. First, the corrections for tissue alignment and distortion were made using a Matlab program. Second, all 2D images were undergone a mathematical smoother processes (rational interpolation) prior to complying the images. As expected, the 3D model clearly showed the distribution of nanoparticles in the eyes following intravitreal injection. Most of the nanoparticles (~80%) accumulated in the retina tissue (Figure 1) and almost no nanoparticle was found in aqueous humor. Interestingly, a small percentage (~1%) of nanoparticles was found in the area of ciliary body.
Here we presented a novel framework to reconstruct 3D eye tissue model for studying and quantifying nanoparticle distribution in eye. This model will allow us to obtain important information for the rational design of nanoparticles or drugs with improved tissue retention and targeting properties.
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