Developing nanocapsules for the targeted drug delivery to the neuroretina

开发用于将靶向药物递送至神经视网膜的纳米胶囊

• 批准号: 426861724
• 负责人: Professor Dr. Francois Paquet-Durand
• 金额: --
• 依托单位: Forschungsinstitut für Augenheilkunde
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/426861724?language=en
• 关键词: Developing; nanocapsules; targeted; drug; delivery

Hereditary retinal degeneration (RD) is a group of rare retinopathies that cause progressive loss of vision. The degeneration and loss of photoreceptors in RD-type diseases is often associated with an excessive activation of cGMP-signalling. Previously, we highlighted the possibility to use inhibitory analogues of cGMP to reduce photoreceptor cell death in vitro and in vivo. The aim of the project is to deliver analogues of cGMP to the retina of RD animal models using a liposomal drug delivery system to reduce side effects and dosing frequency. The liposomes will need to facilitate the transport of the analogues through local, intravitreal injection, while offering protection from degradation of the analogues in the vitreous body and limiting the concentration of analogues needed to induce a positive effect in the retina. Simultaneously, the liposomes should also limit the dose frequency by providing a low drug release and less clearance from the vitreous body compared with free compound. The liposomes will be built from the bottom-up with design choices in mind (e.g. size, surface change, protein conjugation) that can potentially help meet these requirements. The project will address the biodistribution of different types of liposomes in the vitreous body, improve their targeting to photoreceptor cells by means of chemically attached molecular homing devices on the liposome surface, and screen for the mist suitable liposomal delivery system in terms of toxicity, photoreceptor protection, and preservation of retinal function.

遗传性视网膜变性是一组导致进行性失明的罕见视网膜病变。在RD类疾病中，光感受器的退化和丢失通常与cGMP信号的过度激活有关。此前，我们强调了使用cGMP的抑制性类似物在体外和体内减少光感受器细胞死亡的可能性。该项目的目的是使用脂质体给药系统将cGMP类似物输送到RD动物模型的视网膜，以减少副作用和给药频率。脂质体需要通过玻璃体内注射促进类似物的运输，同时提供保护，防止类似物在玻璃体中降解，并限制在视网膜中诱导积极作用所需的类似物的浓度。同时，与游离化合物相比，脂质体还应该通过提供较低的药物释放和较少的玻璃体清除来限制剂量频率。脂质体将自下而上地构建，并考虑到设计选择(例如，大小、表面变化、蛋白质结合)，这些设计可能有助于满足这些要求。该项目将研究不同类型脂质体在玻璃体中的生物分布，通过在脂质体表面化学附着的分子定位装置来提高它们对光感受器细胞的靶向性，并从毒性、光感受器保护和视网膜功能保护的角度筛选适合雾化的脂质体给药系统。