Peptide-based hydrogel co-assembled with antibody-drug for enhanced retinal cell uptake and attenuated experimental autoimmune uveitis

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Mali Dai , Pengyuan Du , Yijing Li , Xiaiting Wang , Jinrun Chen , Hui Liu , Wenqiao Zhang , Jianhong Zhou , Xingyi Li , Yuqin Wang
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引用次数: 0

Abstract

Effective treatment of chronic posterior ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration requires improvements in targeted drug delivery strategies. This study introduces a novel injectable drug delivery system co-assembled with a peptide-based hydrogel and secukinumab (SEK), an IL-17A neutralising monoclonal antibody, targeting retinal pigmented epithelium (RPE) cells. Compared to a SEK solution, the SEK loaded hydrogel significantly enhanced the protein uptake (3.7 times higher) by RPE cells in an inflammatory state after 24 hours of treatment and increased the drug concentration in retinal tissues during 20 days of treatment. A single intravitreal injection of the SEK loaded hydrogel effectively suppressed inflammation in a uveitis model. It also reduced the immunoreactivity of microglia and T helper 17 cells, preserved the integrity of the blood-retina barrier, mitigated retinal cell apoptosis, and facilitated the recovery of the retinal function. This delivery system comprising an antibody-drug co-assembled with a peptide-based hydrogel shows promising potential for targeting the retina and treating complex chronic posterior ocular diseases.

Abstract Image

肽基水凝胶与抗体药物共组装增强视网膜细胞摄取和减轻实验性自身免疫性葡萄膜炎。
有效治疗慢性后眼疾病,如葡萄膜炎、糖尿病视网膜病变和年龄相关性黄斑变性,需要改进靶向给药策略。本研究介绍了一种新的可注射给药系统,该系统由肽基水凝胶和secukinumab (SEK)(一种IL-17A中和单克隆抗体)共同组装,靶向视网膜色素上皮(RPE)细胞。与SEK溶液相比,负载SEK的水凝胶在治疗24 h后显著提高了炎症状态下RPE细胞的蛋白质摄取(3.7倍),并在治疗20 d时增加了视网膜组织中的药物浓度。在葡萄膜炎模型中,单次玻璃体内注射SEK负载的水凝胶可有效抑制炎症。降低小胶质细胞和T辅助17细胞的免疫反应性,保持血视网膜屏障的完整性,减轻视网膜细胞凋亡,促进视网膜功能恢复。这种由抗体-药物与肽基水凝胶共同组装而成的递送系统在靶向视网膜和治疗复杂的慢性后眼疾病方面显示出良好的潜力。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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