Topically administered delivery systems for ophthalmic applications have been studied for the treatment of anterior or posterior eye diseases. However, simultaneous treatment of both anterior and posterior eye diseases has not been explored. In this study, we fabricated a topically administrable polymeric nanoparticle (NP)- based delivery system consisting of pluronic®F-68 shell and polycaprolactone core for the simultaneous treatment of both anterior and posterior eye diseases. These NPs were loaded with pyrrolidine dithiocarbamate (PDTC) or triamcinolone acetonide (TA) separately. The drug loading in NPs was optimized to initially achieve a moderate burst release of PDTC followed by slow and sustained release of both PDTC and TA. The resultant delivery system was studied for its in vivo efficacy in a diabetic retinopathy (DR) and cataract rat model. The results demonstrated that administration of PDTC NPs + TA NPs minimized oxidative stress in lens as evidenced by reduced levels of protein carbonyls and malondialdehyde, and, ameliorated DR complications in retina as evidenced by reduced expression of hypoxia inducible factor-1α along with a reduction in number of neovascular tufts and acellular capillaries. Therefore, delivery of PDTC and TA using PCL-PF68 NPs could be a useful approach for simultaneous treatment of diabetic cataract and DR.

已经研究了用于眼科应用的局部给药递送系统用于治疗前部或后部眼部疾病。然而，尚未探索同时治疗前部和后部眼部疾病。在这项研究中，我们制造了一种可局部给药的基于聚合物纳米颗粒 (NP) 的递送系统，由 pluronic®F-68 壳和聚己内酯核组成，用于同时治疗前部和后部眼部疾病。这些纳米颗粒分别加载了吡咯烷二硫代氨基甲酸酯 (PDTC) 或曲安奈德 (TA)。NPs 中的载药量经过优化，最初实现了 PDTC 的适度突释，然后是 PDTC 和 TA 的缓慢和持续释放。研究了所得的递送系统在体内在糖尿病视网膜病变 (DR) 和白内障大鼠模型中的疗效。结果表明，PDTC NPs + TA NPs 的给药使晶状体中的氧化应激最小化，如蛋白质羰基化合物和丙二醛水平降低所证明的，并且改善了视网膜中的 DR 并发症，如缺氧诱导因子-1α 的表达减少以及新生血管簇和脱细胞毛细血管的数量。因此，使用 PCL-PF68 NPs 递送 PDTC 和 TA 可能是同时治疗糖尿病性白内障和 DR 的有用方法。