Laradji Amine M, Kolesnikov Alexander V, Karakoçak Bedia B, Kefalov Vladimir J, Ravi Nathan
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, United States.
Department of Veterans Affairs, St. Louis Medical Center, St. Louis, Missouri 63106, United States.
ACS Omega. 2021 Feb 22;6(9):6172-6184. doi: 10.1021/acsomega.0c05535. eCollection 2021 Mar 9.
Delivering therapeutics to the posterior segment of the eye is challenging due to various anatomical and physical barriers. While significant improvements have been realized by introducing direct injections to diseased sites, these approaches come with potential side effects that can range from simple inflammation to severe retinal damage. The topical instillation of drugs remains a safer and preferred alternative for patients' compliance. Here, we report the synthesis of penetratin-complexed, redox-responsive hyaluronic acid-based nanogels for the triggered release and delivery of therapeutics to the posterior part of the eye topical application. The synthesized nanogels were shown to release their load only when exposed to a reducing environment, similar to the cytoplasm. As a model drug, visual chromophore analog, 9--retinal, was loaded into nanogels and efficiently delivered to the mouse retina's photoreceptors when applied topically. Electroretinogram measurements showed a partial recovery of photoreceptor function in all treated eyes untreated controls. To the best of our knowledge, this report constitutes the first attempt to use a topically applied triggered-release drug delivery system to target the pigmented layer of the retina, in addition to the first attempt to deliver the visual chromophore topically.
由于各种解剖学和物理屏障，将治疗药物递送至眼后段具有挑战性。虽然通过将直接注射引入患病部位已取得了显著进展，但这些方法存在潜在的副作用，范围从简单的炎症到严重的视网膜损伤。药物的局部滴注对于患者的依从性而言仍然是一种更安全且更受青睐的选择。在此，我们报告了一种穿透肽复合的、氧化还原响应性透明质酸基纳米凝胶的合成，用于通过局部应用将治疗药物触发释放并递送至眼后段。所合成的纳米凝胶显示仅在暴露于类似于细胞质的还原环境时才释放其负载物。作为模型药物，视觉发色团类似物9-顺式视黄醛被载入纳米凝胶中，并在局部应用时有效地递送至小鼠视网膜的光感受器。视网膜电图测量显示，与未治疗的对照相比，所有治疗眼的光感受器功能都有部分恢复。据我们所知，本报告不仅是首次尝试使用局部应用的触发释放药物递送系统靶向视网膜色素层，也是首次尝试局部递送视觉发色团。
