Development of rapamycin-loaded PLGA nanoparticles for treating retinopathy of prematurity.

Abstract

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.