中文摘要
后囊浑浊(PCO)是白内障术后常见并发症,是因位于晶体囊袋赤道部的上皮细胞发生增殖并向后囊移行,继而发生纤维化使后囊皱缩,导致视力再次下降。基于PCO发生机制,本课题组前期分别设计了可定点释放药物[Biomaterials,2016]和体外可控产生活性氧(ROS)[Int J Pharm,2016]的植入体系并获得良好体内疗效。基于前期研究结果,我们拟利用两种治疗模式的优势,将光敏剂与药物以ROS敏感键结合于植入剂中,经激光触发产生ROS,继而触发ROS敏感键释放药物,实现外界可控制ROS与药物在体内的同步释放,进而协同起效。我们在预实验中已设计并合成出以ROS敏感键连接药物的单体CPBA。随后将通过体外细胞及离体囊袋对光触发释放ROS与药物,阐明光照剂量与ROS及药物释放量的相关性及协同机制,构建光触发同步释放ROS和药物的体系,并于体内考察其安全、有效及合理性。探索PCO防治新方法。
英文摘要
Posterior capsule opacification (PCO) is a common complication after cataract surgery. The occurrence of PCO is mainly attributed to the proliferation of residual lens epithelial cells (LECs) in the ambitus of capsule bag. The proliferative LECs would move towards to posterior capsule and become fibrosis, leading to a result of losing vision again. According to the mechanism of PCO, our group had designed relevant systems previously to prevent PCO [Asian J of Pharm Sci, 2013. Biomaterials, 2016. Int J Pharm., 2016]. One of the systems could release drug at specific location [Biomaterials, 2016.] while another one could generate ROS with in-vitro control [Int J Pharm., 2016]. Both of the system showed great potential for PCO prevention. However, they had their own disadvantages respectively. Therefore, this project is going to establish an implant system to integrate the advantages of the two system, which could make PCO prevention more effective and safe. In this project, photosensitizers were loaded and drug was covalently connected to the implant through a ROS-sensitive bond. When irradiated by laser, the implant could generate a large amount of ROS. On one hand, ROS could directly contact with LECs, leading the cells to apoptosis or necrosis. On the other hand, ROS-sensitive bonds would be degraded rapidly with ROS existence and the connected drug would be released. Accordingly, both ROS and drug could be controlled released simultaneously by laser irradiation in vitro and they could play their roles together to make a stronger and safer inhibition to LECs. The monomer CPBA which drug was covalently connected to through ROS-sensitive bonds had been synthesized in our pre-experiment. The synergistic effect of simultaneous releases of ROS and drug would be investigated through MTT assay and ex vivo capsule bag culture. Pharmacodynamics and pharmacokinetics experiments would be conducted to evaluate the efficacy and safety of the implant. We hope this project could put forward a new idea for PCO prevention.
