Biomimetic, Injectable, and Self-Healing Hydrogels with Sustained Release of Ranibizumab to Treat Retinal Neovascularization
Biomimetic, Injectable, and Self-Healing Hydrogels with Sustained Release of Ranibizumab to Treat Retinal Neovascularization
复制标题
具有持续释放雷珠单抗的仿生、可注射和自愈水凝胶可治疗视网膜新生血管
DOI：
10.1021/acsami.2c17626
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发表时间：
2023-01-26
影响因子：
9.5
通讯作者：
Du, Zhaodong
中科院分区：
文献类型：
--
作者：
Duan, Ning;Mei, Li;Du, Zhaodong
视网膜新生血管（Retinal neovascularization，RNV）是缺血性视网膜疾病的典型特征，可导致牵拉性视网膜脱离甚至失明，其中血管内皮细胞生长因子（vascular endothelial cell growth factor，VEGF）起着关键作用。然而，目前用于治疗RNV的大多数抗VEGF药物，如雷珠单抗，由于其玻璃体内半衰期短，需要频繁和重复的玻璃体内注射，这增加了并发症的发生率。本文中，水凝胶玻璃体内药物递送系统（DDS）通过胺化透明质酸与去羧化官能化的Pluronic 127之间的动态席夫碱反应制备，用于缓释雷珠单抗。所制备的水凝胶系统HP@Ran具有良好的可注射性、自修复能力、结构稳定性、细胞相容性和血液相容性。根据体外药物释放研究，该水凝胶系统连续释放模型药物牛血清白蛋白超过56天。重要的是，在体内兔持续性RNV模型中，HP@Ran水凝胶系统连续释放具有生物活性的雷珠单抗超过7周，并且还通过在12周时减少血管渗漏和新血管形成而表现出优于雷珠单抗治疗的上级抗血管生成功效。因此，开发的HP@Ran水凝胶系统具有用于玻璃体内DDS治疗RNV的巨大潜力。
Retinal neovascularization (RNV) is a typical feature of ischemic retinal diseases that can lead to traction retinal detachment and even blindness in patients, in which the vascular endothelial cell growth factor (VEGF) plays a pivotal role. However, most anti-VEGF drugs currently used for treating RNV, such as ranibizumab, need frequent and repeated intravitreal injections due to their short intravitreal half-life, which increases the incidence of complications. Herein, a hydrogel intravitreal drug delivery system (DDS) is prepared by a dynamic Schiff base reaction between aminated hyaluronic acid and aldehyde-functionalized Pluronic 127 for sustained release of ranibizumab. The prepared hydrogel system named HP@Ran exhibits excellent injectability, self-healing ability, structural stability, cytocom-patibility, and blood compatibility. According to an in vitro drug release study, the hydrogel system continuously releases the model drug bovine serum albumin for more than 56 days. Importantly, in an in vivo rabbit persistent RNV model, the HP@Ran hydrogel system continuously releases pharmacologically active ranibizumab for more than 7 weeks and also exhibits superior anti-angiogenic efficacy over ranibizumab treatment by decreasing vascular leakage and neovascularization at 12 weeks. Thus, the developed HP@Ran hydrogel system possesses great potential for intravitreal DDS for the treatment of RNV.