Effect of Particle Size of Polymeric Nanospheres on Intravitreal Kinetics

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_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 eyes completely disappeared within 3 days (t_1/2 = 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.

Inhibitory efficacy of hypoxia-inducible factor 1α short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model

“…43 In vivo, it was reported that PLGA NPs injected into the vitreous of rat eyes followed a 'trans-retinal pathway' and underwent a rapid internalization into the RPE cells layer. 72,76 In our study, we also observed that most NPs encapsulating the pDNA injected in the vitreous localized within the RPE cells, and the expression of the GFP protein was detected as early as the third day after injection and remained detectable for at least 4 weeks by fluorescence microscope.…”

Recent Advances in Ocular Drug Delivery Systems

“…Although a previous study using primates has suggested that molecules exceeding 100 kDa cannot cross the retinal layers into the subretinal space [49], it has been confirmed by immunohistochemical analysis, a full-length, humanized, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (Bevacizumab, Avastin ® , Genentech Inc.), composed of 214 amino acids with a molecular weight of 149 kDa, injected into the vitreous cavity, can penetrate through the sensory retina into retinal pigment epitheliums (RPE), subretinal and choroidal space, in monkey and rabbit [50,51]. In addition, nanometer-sized particles whose mean diameter is below 200 nm can penetrate across the sensory retina into RPE after intravitreal injection in rabbit [52,53].…”

Liposomes and nanotechnology in drug development: focus on ocular targets

“…When fluorescent 2000 nm, 200 nm, and 50 nm nanospheres were injected into the vitreous body of rabbits, the 2000 nm particles were found in the intravitreal cavity and the trabecula, whereas the 200 nm and 50 nm particles were found even inside the retina. 60 When devices that are non-degradable in vivo are used, drug release is stable for a long period, but surgical removal of the device after sustained drug release is generally difficult to achieve. When biodegradable implants are used, they do not need to be removed after sustained drug release; however, in comparison with implants that are non-biodegradable in vivo, intravitreal drug concentration is unstable, and the sustained-release period is shorter.…”