Abstract:
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 β1 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.
摘要:
已经证明地塞米松(DEX)抑制炎性角膜新生血管形成(CNV)。然而,DEX的治疗效果受到常规滴眼液生物利用度差的限制,以及与长期频繁使用相关的激素性青光眼和白内障风险增加.为了解决这些限制,我们开发了一种新的DEX加载,活性氧(ROS)响应,控释纳米凝胶,称为DEX@INHANGs。这种先进的纳米凝胶体系是通过环糊精(CD)和金刚烷(ADA)作为交联力形成超分子主客体复合物而构建的。ROS响应材料的引入,硫酮(TK),确保DEX的受控释放以响应氧化应激,CNV的特征。此外,通过整合素β1融合蛋白的共价结合,纳米凝胶在角膜表面的长时间保留超过8小时,这提高了它的生物利用度。细胞毒性试验表明,DEX@INHANGs对人角膜上皮细胞(HCECs)没有明显的毒性。此外,DEX@INHANGs已被证明在体外有效抑制血管生成。在化学烧伤的兔子模型中,观察到每日一次局部应用DEX@INHANGs可有效抑制CNV。这些结果共同表明,DEX@INHANGs的纳米药物制剂可能为CNV提供有希望的治疗选择,提供显著的优势,如减少给药频率和提高患者的依从性。