Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles
Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles
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DOI：
10.1167/iovs.02-1068
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发表时间：
2003-08-01
影响因子：
4.4
通讯作者：
Behar-Cohen, FF
中科院分区：
文献类型：
--
作者：
Bourges, JL;Gautier, SE;Behar-Cohen, FF
目的.研究聚乳酸（PLA）纳米粒（NP）在眼内组织中的定位动力学，并评价其释放包封材料的潜力。进行包封Rh-6 G（Rh）或尼罗红（Nr）的NP悬浮液（2.2 mg/mL）的单次玻璃体内注射（5穆尔）。在不同时间处死动物，通过环境扫描电子显微镜（ESEM）、共聚焦显微镜、光学显微镜组织学、荧光显微镜和免疫组织化学研究眼内组织中的NPs定位。注射空白NP、游离Rh或PBS溶液的眼睛用作对照。ESEM显示纳米颗粒从注射部位流入玻璃体腔，并快速沉积在内界膜上。组织学证明了注射眼的解剖完整性，并且没有显示毒性作用。注射后6小时在睫状体中观察到轻度炎性细胞浸润，18 - 24小时在后玻璃体和视网膜中观察到轻度炎性细胞浸润。炎症强度在48小时时显著降低。共聚焦和荧光显微镜和免疫组织化学显示，一个transretinal运动的NPs逐渐发生，后来在RPE细胞的本地化。包裹在注射的NP内的Rh扩散并染色视网膜和RPE细胞。PLA NPs在玻璃体内注射4个月后仍存在于RPE细胞内。玻璃体内注射PLA纳米颗粒似乎导致跨视网膜运动，优先定位在RPE细胞中。包裹的Rh从NP扩散并染色神经视网膜和RPE细胞。这些发现支持了特异性靶向这些组织是可行的这一观点。此外，在单次注射后4个月，RPE细胞内存在NP，这表明可以实现药物的稳定和连续递送。
PURPOSE. To study the kinetics of polylactide (PLA) nanoparticle (NP) localization within the intraocular tissues and to evaluate their potential to release encapsulated material.METHODS. A single intravitreous injection (5 muL) of an NP suspension (2.2 mg/mL) encapsulating either Rh-6G (Rh) or Nile red (Nr) was performed. Animals were killed at various times, and the NPs localization within the intraocular tissues was studied by environmental scanning electron microscopy (ESEM), confocal microscopy, light microscopy histology, fluorescence microscopy, and immunohistochemistry. Eyes injected with blank NPs, free Rh, or PBS solution were used as the control.RESULTS. ESEM showed the flow of the NPs from the site of injection into the vitreous cavity and their rapid settling on the internal limiting membrane. Histology demonstrated the anatomic integrity of the injected eyes and showed no toxic effects. A mild inflammatory cell infiltrate was observed in the ciliary body 6 hours after the injection and in the posterior vitreous and retina at 18 to 24 hours. The intensity of inflammation decreased markedly by 48 hours. Confocal and fluorescence microscopy and immunohistochemistry showed that a transretinal movement of the NPs was gradually taking place with a later localization in the RPE cells. Rh encapsulated within the injected NPs diffused and stained the retina and RPE cells. PLA NPs were still present within the RPE cells 4 months after a single intravitreous injection.CONCLUSIONS. Intravitreous injection of PLA NPs appears to result in transretinal movement, with a preferential localization in the RPE cells. Encapsulated Rh diffuses from the NPs and stains the neuroretina and the RPE cells. The findings support the idea that specific targeting of these tissues is feasible. Furthermore, the presence of the NPs within the RPE cells 4 months after a single injection shows that a steady and continuous delivery of drugs can be achieved.