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Ocular disposition and tolerance of ganciclovir-loaded albumin nanoparticles after intravitreal injection in rats.

机译:大鼠玻璃体内注射更昔洛韦负载白蛋白纳米粒子的眼部处置和耐受性。

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摘要

Cytomegalovirus (CMV) infection mainly affects endothelial cells of ocular vessels, optic nerve and the retina, resulting in direct or autoimmune damages, uveoretinitis and disturbed vision. The use of colloidal carriers for the intravitreal delivery of ganciclovir may prolong its residence in the eye, minimizing the opacification observed for macroscopic implants. The aim of this work was to evaluate the ocular toxicity induced by the prolonged presence of ganciclovir-loaded bovine serum albumin nanoparticles after their intravitreal injection. The intraocular disposition of these carriers was also studied by immunochemistry. Two weeks post-injection, a significant amount of nanoparticles remained in the vitreous cavity, mainly in a thin layer overlying the retina and in the area close to the blood aqueoUs barrier. Their prolonged residence in the eve seemed to be well tolerated and the histological evaluation of the retina, mainly the photoreceptor layer, and adjacent tissues revealed the absence of inflammatory reactions or alterations in the tissue architecture (i.e. cellular infiltrations or vascular inflammation). In addition, nanoparticles neither alter the expression and distribution of arrestin and rhodopsin autoantigens nor the mineralocorticoid receptor. In summary, the vision was not affected by autoimmune phenomena or alterations in the behavior of ophthalmic cells due to the intravitreal injection of these nanoparticles.
机译:巨细胞病毒(CMV)感染主要影响眼血管,视神经和视网膜的内皮细胞,导致直接或自身免疫损害,葡萄膜视网膜炎和视力障碍。将胶体载体用于更昔洛韦的玻璃体内给药可延长其在眼中的停留时间,从而最大程度地减少了肉眼可见的植入物的混浊。这项工作的目的是评估玻璃体内注射后更长时间服用更昔洛韦的牛血清白蛋白纳米粒子引起的眼毒性。还通过免疫化学研究了这些载体的眼内处置。注射后两周,大量的纳米粒子保留在玻璃体腔中,主要保留在视网膜上的薄层以及靠近血水屏障的区域。它们在前夕的长期居住似乎被很好地耐受,并且视网膜(主要是感光层)和邻近组织的组织学评估显示,在组织结构中不存在炎症反应或改变(即细胞浸润或血管炎症)。另外,纳米颗粒既不改变抑制素和视紫红质自身抗原的表达和分布,也不改变盐皮质激素受体。总之,由于这些纳米粒子的玻璃体内注射,视力不受自身免疫现象或眼细胞行为改变的影响。

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