视网膜
视网膜变性
体内
脉络膜新生血管
视网膜
药理学
离体
黄斑变性
癌症研究
化学
医学
眼科
生物
神经科学
生物技术
作者
Congyan Liu,Wenting Su,Xi Jiang,Yanli Lv,Fei Kong,Qin Chen,Qun Zhang,Huangqin Zhang,Yuping Liu,Xiaoqi Li,Xiaoling Xu,Yan Chen,Ding Qu
标识
DOI:10.1002/adhm.202303659
摘要
Abstract Sustainable retinal codelivery poses significant challenges technically, although it is imperative for synergistic treatment of wet age‐related macular degeneration (wAMD). Here, a microemulsion‐doped hydrogel (Bor/PT‐M@TRG) is engineered as an intravitreal depot composing of temperature‐responsive hydrogel (TRG) and borneol‐decorated paeoniflorin (PF) & tetramethylpyrazine (TMP)‐coloaded microemulsions (Bor/PT‐M). Bor/PT‐M@TRG, functioning as the “ammunition depot”, resides in the vitreous and continuously releases Bor/PT‐M as the therapeutic “bullet”, enabling deep penetration into the retina for at least 21 days. A single intravitreal injection of Bor/PT‐M@TRG yields substantial reductions in choroidal neovascularization (CNV, a hallmark feature of wAMD) progression and mitigates oxidative stress‐induced damage in vivo. Combinational PF&TMP regulates the ′ROS/Nrf2/HO‐1″ pathway and blocks the ′HIF‐1α/VEGF″ signaling in retina, synergistically cutting off the loop of CNV formation. Utilizing fluorescence resonance energy transfer (FRET) and LC‐MS/MS techniques, we present compelling multifaceted evidence of sustainable retinal codelivery spanning formulations, ARPE‐19 cells, in vivo eye balls, and ex vivo section/retina‐choroid complex cell levels. Such codelivery approach is elucidated as the key driving force behind the exceptional therapeutic outcomes of Bor/PT‐M@TRG. These findings highlight the significance of sustainable retinal drug codelivery and rational combination, providing critical insights to advance wAMD therapy and inspire the development of innovative retinal drug delivery strategies. This article is protected by copyright. All rights reserved
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