Biodegradable serpin-peptide-carrying nano- and microparticles for wet AMD

描述（由申请人提供）：湿性年龄相关性黄斑变性（AMD）是美国60岁以上患者严重视力丧失和失明的最常见原因。视网膜下新生血管形成是导致最严重视力丧失的原因。新发现的肽SP 6001通过多种抗血管生成机制发挥作用，有望治疗湿性AMD。小肽作为治疗剂具有许多有利的特性，例如高特异性和低毒性，但它们的主要缺点是它们的生物活性低。 半衰期短。为了克服这种可能的限制，将构建一种新的反向反转形式的肽，并通过将其封装在聚合物颗粒系统中来保护其免受降解。该颗粒递送系统将确保新型抗血管生成肽沿着在眼内的安全和有效递送以及其受控释放。将合成新的生物材料和颗粒制剂，然后对颗粒性质、肽释放和体外生物活性进行评价。在对人视网膜内皮细胞的实验之后，将在湿性AMD的小鼠模型中体内测试颗粒/肽系统。将反向转化肽与标准和乱序肽进行比较，并评价颗粒制剂的功效4个月。还将进行体外测定以鉴定肽作用的受体以及这些受体在正常条件下和AMD条件下在眼中的分布。一种新的有效的治疗方式，可以抑制VEGF介导的和非VEGF介导的血管生成途径，并可以减少必要的玻璃体内注射的频率，将显着改善目前使用的治疗AMD。

DESCRIPTION (provided by applicant): Wet age-related macular degeneration (AMD) is the most prevalent cause of severe vision loss and blindness in patients over the age of 60 in the US. Subretinal neovascularization is responsible for most severe loss of vision. A newly discovered peptide, SP6001, is promising for treating wet AMD as it works through multiple antiangiogenic mechanisms. Small peptides possess many advantageous characteristics as therapeutic agents, such as high specificity and low toxicity, but their main disadvantage is their short half-life. To counter this possible limitation, a novel retroinverted version of the peptide ill be constructed and it will be protected from degradation by being encapsulated within a polymeric particle system. The particle delivery systems will ensure safe and effective delivery of the novel antiangiogenic peptide along with its controlled release within the eye. New biomaterials and particle formulations will be synthesized and then particle properties, peptide release, and biological activity in vitro evaluated. Following experiments on human retinal endothelial cells, the particle/peptide systems will be tested in vivo in mouse models for wet AMD. Retroinverted peptide will be compared to standard and scrambled peptide and efficacy of particle formulations will be evaluated for 4 months. In vitro assays will also be performed to identify the receptors that the peptide acts on and the distribution of these receptors in the eye under normal conditions and under AMD conditions. A new validated treatment modality that can inhibit both VEGF-mediated and non-VEGF- mediated angiogenic pathways and that can reduce the frequency of necessary intravitreal injections would significantly improve the currently used treatments for AMD.