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Long‐term therapeutic effect in nonhuman primate eye from a single injection of anti‐VEGF controlled release hydrogel

机译:单次注射抗VEGF控释水凝胶对非人类灵长类动物眼的长期治疗作用

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摘要

Wet age‐related macular degeneration (wet‐AMD) is a leading cause of irreversible blindness. Current treatment of AMD requires monthly intravitreal injection, which is difficult to be implemented in many parts of the world. In recent years, controlled release of anti‐vascular endothelial growth factor (VEGF) therapeutics has attracted intense research interest aiming to reduce the injection frequency to one or two times per year. In this study, we evaluated the in vivo pharmacokinetics and the long‐term therapeutic efficacy of an in situ hydrogel encapsulating an anti‐VEGF antibody in nonhuman primates. We show that after a single injection of anti‐VEGF controlled release hydrogel, a relatively constant concentration of drug can be maintained in the monkey eye for at least 5 months and the dose was sufficient for the treatment of recurrent choroidal neovascularization induced by repeat laser photocoagulation in monkeys. Our result suggested that when formulated into a controlled release formulation, a single dose of anti‐VEGF may be sufficient for a half‐year treatment and controlled release may be a suitable strategy to reduce the injection frequency in the treatment of AMD in human.
机译:与年龄相关的湿性黄斑变性(wet-AMD)是不可逆性失明的主要原因。当前对AMD的治疗需要每月玻璃体内注射,这在世界许多地方都难以实施。近年来,抗血管内皮生长因子(VEGF)治疗药物的控释引起了强烈的研究兴趣,旨在将注射频率降低到每年一到两次。在这项研究中,我们评估了在非人类灵长类动物体内包裹抗VEGF抗体的原位水凝胶的体内药代动力学和长期治疗效果。我们显示,单次注射抗VEGF控释水凝胶后,在猴眼中可以维持相对恒定的药物浓度至少5个月,并且该剂量足以治疗由重复激光光凝引起的复发性脉络膜新血管形成在猴子里。我们的结果表明,当制成控释制剂时,单剂抗VEGF可能足以进行半年治疗,而控释则可能是降低人AMD治疗中注射频率的合适策略。

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