Shi Hui, Ju Yuqiao, Chang Qing, Cen Lian
Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology. No.130 Mei Long Road, Shanghai, 200237, China.
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
Biomater Sci. 2025 Jul 8;13(14):3929-3941. doi: 10.1039/d5bm00555h.
With the increasing incidence of retinopathy of prematurity (ROP) and the gradual emergence of side effects associated with existing treatments, the development of novel nano-therapy strategies for ROP has become critically urgent. The aim of the current study was to explore the possibility of developing PLGA nanoparticles loaded with rapamycin (RPM) (RPM-PLGA NPs) for the sustained release of RPM as a nano-therapy for ROP intervention. RPM-PLGA NPs were prepared using a nanoprecipitation method, and their physicochemical properties were characterized. The safety profile and therapeutic efficacy of RPM-PLGA NPs were evaluated in BV2, HUVEC cells and in an oxygen-induced retinopathy (OIR) mouse model. RPM-PLGA NPs of 144.23 ± 3.40 nm, a polydispersity index of 0.05 ± 0.02, an encapsulation efficiency of 81.39%, and a drug loading capacity of 16.28% were successfully prepared. The sustained and gradual release of RPM from these NPs was achieved for over 35 days. It was demonstrated that RPM-PLGA NPs had no significant effect on the viability and migration of BV2 and HUVECs. In the oxygen-induced OIR model, RPM-PLGA NPs significantly reduced the areas of vaso-obliteration and pathological neovascularization in the mouse retina, showing superior therapeutic effects compared to RPM alone. These findings validated the feasibility of RPM-PLGA NPs as an intravitreal injection for the treatment of ROP. It is believed that the current study could provide promising experimental data for nano-therapy as an effective and superior treatment for ROP with few side effects.
随着早产儿视网膜病变（ROP）发病率的不断上升以及现有治疗方法相关副作用的逐渐显现，开发针对ROP的新型纳米治疗策略已变得极为迫切。本研究的目的是探索开发负载雷帕霉素（RPM）的聚乳酸-羟基乙酸共聚物纳米颗粒（RPM-PLGA NPs）以实现RPM持续释放作为ROP干预纳米治疗方法的可能性。采用纳米沉淀法制备RPM-PLGA NPs，并对其理化性质进行表征。在BV2、人脐静脉内皮细胞（HUVEC）以及氧诱导视网膜病变（OIR）小鼠模型中评估RPM-PLGA NPs的安全性和治疗效果。成功制备出粒径为144.23±3.40 nm、多分散指数为0.05±0.02、包封率为81.39%且载药量为16.28%的RPM-PLGA NPs。这些纳米颗粒实现了RPM超过35天的持续、缓慢释放。结果表明，RPM-PLGA NPs对BV2和HUVEC的活力和迁移没有显著影响。在氧诱导的OIR模型中，RPM-PLGA NPs显著减少了小鼠视网膜血管闭塞和病理性新生血管的面积，与单独使用RPM相比显示出更好的治疗效果。这些发现证实了RPM-PLGA NPs玻璃体内注射治疗ROP的可行性。相信本研究可为纳米治疗作为一种有效且副作用少的ROP优越治疗方法提供有前景的实验数据。
