Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, India; The Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur 208016, India.
Biochemistry Division, National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500007, India.
Int J Pharm. 2021 Oct 25;608:121045. doi: 10.1016/j.ijpharm.2021.121045. Epub 2021 Sep 2.
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.
用于眼部应用的局部给药系统已被研究用于治疗前眼或后眼疾病。然而，尚未探索同时治疗前眼和后眼疾病。在这项研究中，我们制备了一种可局部给药的聚合物纳米粒子（NP）给药系统，由普朗尼克® F-68 壳和聚己内酯核组成，用于同时治疗前眼和后眼疾病。这些 NPs 分别负载吡咯烷二硫代氨基甲酸盐（PDTC）或曲安奈德（TA）。通过优化载药，NP 最初实现 PDTC 的适度突释，随后 PDTC 和 TA 缓慢持续释放。所得的给药系统在糖尿病视网膜病变（DR）和白内障大鼠模型中进行了体内疗效研究。结果表明，PDTC NPs+TA NPs 的给药最大限度地减少了晶状体中的氧化应激，这表现为蛋白质羰基和丙二醛水平降低，并且改善了视网膜中的 DR 并发症，表现为缺氧诱导因子-1α 的表达减少以及新生血管丛和无细胞毛细血管的数量减少。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 的有效方法。
