Sustained-Release Microspheres of Rivoceranib for the Treatment of Subfoveal Choroidal Neovascularization

Abstract

The wet type of age-related macular degeneration (AMD) accompanies the subfoveal choroidal neovascularization (CNV) caused by the abnormal extension or remodeling of blood vessels to the macula and retinal pigment epithelium (RPE). Vascular endothelial growth factor (VEGF) is known to play a crucial role in the pathogenesis of the disease. In this study, we tried to repurpose an investigational anticancer drug, rivoceranib, which is a selective inhibitor of VEGF receptor-2 (VEGFR2), and evaluate the therapeutic potential of the drug for the treatment of wet-type AMD in a laser-induced CNV mouse model using microsphere-based sustained drug release formulations. The PLGA-based rivoceranib microsphere can carry out a sustained delivery of rivoceranib for 50 days. When administered intravitreally, the sustained microsphere formulation of rivoceranib effectively inhibited the formation of subfoveal neovascular lesions in mice.

Fabrication of polymeric microspheres for biomedical applications

“…For example, PLGA microspheres loaded with anticancer drugs were prepared through an oil-in-water emulsification process. 125 The fabrication parameters such as emulsification speed exert an important effect on the morphology of the PLGA microspheres. Under the relatively high emulsification speed (2000 rpm), the smaller size of microspheres and increased surface area were produced in comparison with the lower emulsification speed (1500 rpm), which led to faster drug release.…”

Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball

“…Hence, Rivoceranib can effectively reduce retinal vascular leakage and corneal neovascularization [ 138 , 139 ]. Successful vitreous delivery using PLGA delivery systems can inhibit neovascularization in the avascular zone of the fovea (subfoveal CNV) [ 117 ]. Previous experiments have demonstrated the therapeutic effect of inhibiting VEGF in a laser-induced CNV rat model using a microsphere hydrogel drug delivery system [ 140 ].…”

Development and optimization of sustained release triptolide microspheres

“…To address these limitations, a sustained release drug delivery system (DDS) for injection, which can deliver a relatively constant dose of triptolide for a long period of time, may provide an alternative to solve the aforementioned problems to some extent. Microspheres are innovative DDSs that possess favorable features and have been studied widely over three decades [ 14 ]. Microspheres can be classified into two types, biodegradable and nonbiodegradable, and biodegradable microspheres are preferable in practical applications.…”