Lee Simin, Park Jun Young, Hong Hye Kyoung, Son Joo Young, Kim Byungwook, Chung Jae Yong, Woo Se Joon, Park Ki Dong
Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.
Asian J Pharm Sci. 2024 Oct;19(5):100947. doi: 10.1016/j.ajps.2024.100947. Epub 2024 Aug 8.
Retinal vascular disease is the leading cause of visual impairment. Although intravitreal drug injections are the most suitable approach for addressing retinal disorders, existing clinical treatments necessitate repeated administration, imposing a substantial burden on patients with various intraocular complications. This study introduces an injectable and biodegradable hyaluronan microgel (Hm)-embedded gelatin-poly(ethylene glycol)-tyramine hydrogel (HmGh) designed for sustained intravitreal ranibizumab (RBZ) delivery to reduce patient burden and minimize the side effects associated with frequent injections. Hm exhibited a controlled RBZ loading capacity and release profile. HmGh effectively controlled the initial burst release and overall release profile. Cytocompatibility and cellular drug efficacy were also demonstrated. In an animal study, HmGh maintained RBZ concentrations in the vitreous and retina for >120 d. Pharmacokinetic studies showed that the half-life of RBZ-loaded HmGh in the vitreous and retina was 2.55 and 2.05 times longer than that of RBZ-loaded Hm, respectively, and 9.58 and 38.46 times longer than that of RBZ solution, respectively. Importantly, the initial RBZ elimination from HmGh to the aqueous humor was significantly reduced compared to that from the Hm and RBZ solutions. Intraocular degradation and safety were comprehensively evaluated using fundus imaging and histological analyses. In conclusion, this injectable microgel-embedded hydrogel formulation is a promising prolonged drug delivery system for treating various posterior segment eye diseases.
视网膜血管疾病是视力损害的主要原因。尽管玻璃体内药物注射是治疗视网膜疾病最合适的方法，但现有的临床治疗需要重复给药，给患有各种眼内并发症的患者带来了沉重负担。本研究介绍了一种可注射且可生物降解的透明质酸微凝胶（Hm）包埋的明胶-聚（乙二醇）-酪胺水凝胶（HmGh），其设计用于玻璃体内雷珠单抗（RBZ）的持续递送，以减轻患者负担并将与频繁注射相关的副作用降至最低。Hm表现出可控的RBZ负载能力和释放曲线。HmGh有效地控制了初始突释和整体释放曲线。还证明了细胞相容性和细胞药物疗效。在一项动物研究中，HmGh在玻璃体和视网膜中维持RBZ浓度超过120天。药代动力学研究表明，负载RBZ的HmGh在玻璃体和视网膜中的半衰期分别比负载RBZ的Hm长2.55倍和2.05倍，分别比RBZ溶液长9.58倍和38.46倍。重要的是，与Hm和RBZ溶液相比，HmGh向房水的初始RBZ消除显著减少。使用眼底成像和组织学分析对眼内降解和安全性进行了全面评估。总之，这种可注射的微凝胶包埋水凝胶制剂是一种有前途的长效药物递送系统，用于治疗各种后段眼部疾病。
