Effect of particle size of polymeric nanospheres on intravitreal kinetics

In this study, we injected nanospheres containing a fluorescein derivative into the vitreous cavity of pigmented rabbit eyes and evaluated their intra ocular kinetics as drug carriers in vivo. Polystyrene nanospheres (2 mum, 2 00 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 mug/ml equivalent to sodium fluore scein. The suspension of nanospheres was injected once into the vitreous ca vity of unilateral eyes of pigmented rabbits. A sodium fluorescein solution of the same concentration was injected once into the vitreous cavity of th e other eye as the control. The intraocular kinetics of nanospheres was eva luated by measuring vitreous fluorescence using a scanning fluorophotometer . To investigate elimination pathways of nanospheres in detail, serial cros s-sections of the eyes were examined with a fluorescence microscope. The fl uorescence derived from nanospheres was observed in the vitreous cavity for over 1 month (2 mum: t(1/2) = 5.4 +/- 0.8 days, 200 nm: t(1/2) = 8.6 +/- 0 .7 days, 50 nm: t(1/2) = 10.1 +/- 1.8 days), whereas that in the control ey es completely disappeared within 3 days (t(1/2) = 7.8 +/- 0.7 h). The elimi nation half-life from the vitreous cavity correlated well with the particle diameter (r = -0.997, P = 0.007). Histological studies using a fluorescenc e microscope revealed that nanospheres with a diameter of 2 mum were seen i n the vitreous cavity and trabecular meshwork, while nanospheres with a dia meter of smaller than 200 nm were also observed in the retina as well as th ese tissues. Our findings indicated that nanospheres may be beneficial as a drug carrier to the retina, vitreous and trabecular meshwork. Copyright (C ) 2001 S. Karger AG, Basel.