Abstract
In this study, we injected nanospheres containing a fluorescein derivative into the vitreous cavity of pigmented rabbit eyes and evaluated their intraocular kinetics as drug carriers in vivo. Polystyrene nanospheres (2 µm, 200 nm and 50 nm in diameter) containing a fluorescein derivative were used in this study. A suspension of each particle was prepared by diluting with distilled water at a concentration of 10 µg/ml equivalent to sodium fluorescein. The suspension of nanospheres was injected once into the vitreous cavity of unilateral eyes of pigmented rabbits. A sodium fluorescein solution of the same concentration was injected once into the vitreous cavity of the other eye as the control. The intraocular kinetics of nanospheres was evaluated by measuring vitreous fluorescence using a scanning fluorophotometer. To investigate elimination pathways of nanospheres in detail, serial cross-sections of the eyes were examined with a fluorescence microscope. The fluorescence derived from nanospheres was observed in the vitreous cavity for over 1 month (2 µm: t<sub>1/2</sub> = 5.4 ± 0.8 days, 200 nm: t<sub>1/2</sub> = 8.6 ± 0.7 days, 50 nm: t<sub>1/2</sub> = 10.1 ± 1.8 days), whereas that in the control eyes completely disappeared within 3 days (t<sub>1/2</sub> = 7.8 ± 0.7 h). The elimination half-life from the vitreous cavity correlated well with the particle diameter (r = –0.997, p = 0.007). Histological studies using a fluorescence microscope revealed that nanospheres with a diameter of 2 µm were seen in the vitreous cavity and trabecular meshwork, while nanospheres with a diameter of smaller than 200 nm were also observed in the retina as well as these tissues. Our findings indicated that nanospheres may be beneficial as a drug carrier to the retina, vitreous and trabecular meshwork.
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