Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization

作者全名："Xiang, Yongguo; Qiu, Zhu; Ding, Yuanfu; Du, Miaomiao; Gao, Ning; Cao, Huijie; Zuo, Hangjia; Cheng, Hong; Gao, Xiang; Zheng, Shijie; Wan, Wenjuan; Huang, Xiaobei; Hu, Ke"

作者地址："[Xiang, Yongguo; Du, Miaomiao; Gao, Ning; Cao, Huijie; Zuo, Hangjia; Cheng, Hong; Gao, Xiang; Zheng, Shijie; Wan, Wenjuan; Hu, Ke] Chongqing Med Univ, Chongqing Eye Inst,Affiliated Hosp 1,Chongqing Bra, Chongqing Branch Municipal Div Natl Clin Res Ctr O, Chongqing Key Lab Prevent & Treatment Major Blindi, 1 Youyi Rd, Chongqing 400010, Peoples R China; [Qiu, Zhu] Chongqing Med Univ, Key Lab Mol Oncol & Epigenet, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400010, Peoples R China; [Ding, Yuanfu] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa 999078, Peoples R China; [Huang, Xiaobei] Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, 266 Fangzheng Ave, Chongqing 400714, Peoples R China"

通信作者："Hu, K (通讯作者)，Chongqing Med Univ, Chongqing Eye Inst,Affiliated Hosp 1,Chongqing Bra, Chongqing Branch Municipal Div Natl Clin Res Ctr O, Chongqing Key Lab Prevent & Treatment Major Blindi, 1 Youyi Rd, Chongqing 400010, Peoples R China.; Huang, XB (通讯作者)，Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, 266 Fangzheng Ave, Chongqing 400714, Peoples R China."

来源：JOURNAL OF CONTROLLED RELEASE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001326283400001

JCR分区：Q1

影响因子：10.8

年份：2024

卷号：372

期号：　

开始页：874

结束页：884

文献类型：Article

关键词：Nanogel; Host-guest interaction; Corneal neovascularization; Dexamethasone; Reactive oxygen species; Stimuli-responsive

摘要："Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin beta 1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance."

基金机构："National Natural Science Foundation of China [81970832, 82371098]; Project Foundation of Chongqing Science and Technology Commission of China [CSTB2023NSCQ-MSX1077, CSTC2021jscx-gksb-N0017, cstc2021jcyj-msxmX0967]; Chongqing Talent Plan ""Contract pro-gram"" [cstc2022ycjh-bgzxm0121]"

基金资助正文："<B>Acknowledgments</B> This work was supported by the National Natural Science Foundation of China (Grant nos. 81970832, and 82371098) , the Project Foundation of Chongqing Science and Technology Commission of China (Grant nos. CSTB2023NSCQ-MSX1077, CSTC2021jscx-gksb-N0017, and cstc2021jcyj-msxmX0967) and Chongqing Talent Plan ""Contract pro-gram"" (Grant no. cstc2022ycjh-bgzxm0121) ."