School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India.
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India.
Int J Biol Macromol. 2023 Jan 1;224:810-830. doi: 10.1016/j.ijbiomac.2022.10.168. Epub 2022 Oct 24.
Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.
糖尿病性视网膜病变（DR）是糖尿病的慢性并发症之一。它包括视网膜血管的损伤。如果不治疗，会导致视力丧失。现有的 DR 治疗策略既昂贵又具有侵入性，并且在管理过程中需要专业知识。因此，需要开发一种非侵入性的局部制剂，它可以穿透视网膜的后段并治疗受损的视网膜血管。此外，它还应该提供持续释放。近年来，新型药物传递系统（NDDS）已被探索用于治疗 DR，并取得了成功。在这项研究中，通过改良的熔融乳化-超声法制备了壳聚糖（CS）修饰的 5-氟尿嘧啶纳米结构脂质载体（CS-5-FU-NLCs），并通过 Box-Behnken 设计进行了优化。CS-5-FU-NLCs 的粒径、多分散指数、Zeta 电位和包封效率分别为 163.2±2.3nm、0.28±1.52、21.4±0.5mV 和 85.0±0.2%。体外药物释放和离体渗透研究证实，CS-5-FU-NLCs 具有更高和更持续的药物释放。HET-CAM 模型确保了 CS-5-FU-NLCs 的非刺激性。CS-5-FU-NLCs 的体内眼部研究通过 CAM 模型和糖尿病性视网膜病变诱导的大鼠模型证实了 5-FU 的抗血管生成作用，表明 5-FU 成功递送到了视网膜。
