Despite years of effort, sustained delivery of protein therapeutics remains an unmet need due to three primary challenges - dose, duration, and stability. The work presented here provides a design methodology for polycaprolactone reservoir-based thin film devices suitable for long-acting protein delivery to the back of the eye. First, the challenge of formulating highly concentrated protein in a device reservoir was addressed by improving stability with solubility-reducing excipients. Next, predictive correlations between design parameters and device performance were developed to provide a methodology to achieve a target product profile. Prototype devices were designed using this methodology to achieve desired device size, release rate, therapeutic payload, and protein stability, assessed by in vitro studies. Finally, prototype tolerability was established in a non-human primate model. The design methodology presented here is widely applicable to reservoir-based sustained delivery devices for proteins and provides a general device design framework.

中文翻译：

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用于持续释放眼内递送的蛋白质治疗剂的装置设计方法和配方。

尽管经过多年的努力，由于三个主要挑战——剂量、持续时间和稳定性，持续提供蛋白质治疗的需求仍然未得到满足。这里介绍的工作提供了一种基于聚己内酯储库的薄膜装置的设计方法，适用于将长效蛋白质输送到眼睛后部。首先，通过使用降低溶解度的赋形剂提高稳定性来解决在设备储库中配制高浓度蛋白质的挑战。接下来，开发了设计参数和器件性能之间的预测相关性，以提供实现目标产品概况的方法。使用这种方法设计原型设备，以实现所需的设备尺寸、释放速率、治疗有效负载和蛋白质稳定性，并通过体外研究进行评估。最后，在非人类灵长类动物模型中建立了原型耐受性。这里提出的设计方法广泛适用于基于储库的蛋白质持续输送装置，并提供了通用的装置设计框架。