Ger Tzong-Yun, Yang Chia-Jung, Bui Hoang Linh, Lue Shingjiang Jessie, Yao Chun-Hsu, Lai Jui-Yang
Department of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan; Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
Department of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan.
Carbohydr Polym. 2025 Mar 15;352:123164. doi: 10.1016/j.carbpol.2024.123164. Epub 2024 Dec 17.
In this study, we aimed to develop ion-responsive and biocompatible alginate-capped nanoceria (Ce-ALG) for β-1,3-glucan (i.e., wound healing agent) delivery and corneal abrasion (CA) treatment. Specifically, alginate coatings confer the metallic nanocarriers with enhanced mucoadhesion, prolonged precorneal retention via hydrogen bonding, and improved viscosity. Additionally, increasing alginate grafting amount increased the surface stiffness and facilitated cellular uptake, thereby increasing bioactive potential of the nanocarriers. On the other hand, a stable egg-box structure formed by alginate complexation with Ca not only heightened the encapsulation efficiency of β-1,3-glucan, but also provided sustained drug release during ion exchange with Na in tears. In vitro studies demonstrated an improvement in pharmacological wound closure, as evidenced by the accelerated migration and proliferation of corneal epithelial cells exposed to β-1,3-glucan-loaded Ce-ALG. In a rabbit model of CA, a single dose of the eye drop formulation with the maximum grafting amount of alginate remarkably reduced epithelial injury area by ~99 % at 5 days post-instillation, which was 45- and 53-fold more effective in wound area reduction than that of Ce and ketorolac (an analgesic commonly used for managing CA) groups, respectively. Overall, surface functionalization with alginate greatly enhanced the ocular bioavailability of nanotherapeutics for corneal epithelial injury recovery.
在本研究中，我们旨在开发用于递送β-1,3-葡聚糖（即伤口愈合剂）和治疗角膜擦伤（CA）的离子响应性且具有生物相容性的藻酸盐包覆纳米氧化铈（Ce-ALG）。具体而言，藻酸盐涂层赋予金属纳米载体增强的粘膜粘附性、通过氢键延长角膜前滞留时间以及改善粘度。此外，增加藻酸盐接枝量会增加表面硬度并促进细胞摄取，从而提高纳米载体的生物活性潜力。另一方面，藻酸盐与钙络合形成的稳定蛋盒结构不仅提高了β-1,3-葡聚糖的包封效率，还在与泪液中的钠进行离子交换时实现了药物的持续释放。体外研究表明，暴露于负载β-1,3-葡聚糖的Ce-ALG的角膜上皮细胞迁移和增殖加速，这证明了其在药理伤口闭合方面有所改善。在CA的兔模型中，单剂量使用藻酸盐接枝量最大的滴眼剂配方，在滴注后5天，上皮损伤面积显著减少了约99%，在减少伤口面积方面分别比Ce组和酮咯酸（一种常用于治疗CA的镇痛药）组有效45倍和53倍。总体而言，用藻酸盐进行表面功能化大大提高了纳米治疗剂对角膜上皮损伤恢复的眼部生物利用度。
