Vascular endothelial growth factor (VEGF) is a protein produced in the body to stimulate the formation of new blood vessels. Anti-VEGF agents have been widely used to treat several eye diseases such as proliferative diabetic retinopathy, age-related macular degeneration and retinal vein occlusion. However, their oral/systemic administration is associated with severe side effects such as hypertension and renal disorders, thus limiting their therapeutic potential for ocular diseases. Therefore, there is a need to develop an approach that will maximize the local concentration of a drug at a target site while also minimizing the systemic exposure.
Our inventors have developed PLGA encapsulated Sunitinib nanoparticles for the effective treatment of several eye diseases including diabetic retinopathy, age-related macular degeneration and retinal vein occlusion. This technology was incorporated into a PLGA thermo-reversible gel to further increase the residence time after injection into the eye, therefore allowing for extended drug release. With intravitreal injections, these nanoparticles exhibit reduced side effects compared to current oral/systemic administration methods. Moreover, the encapsulated Sunitinib can inhibit VEGF and other growth factor receptors. Inhibition of these receptors may provide a more effective treatment option for several eye diseases than currently available drugs such as aflibercept, bevacizumab, and orranibizumab. Further, this technology does not require the co-administration of additional intravitreal agents.
The nanoparticles exhibited reduced % VEGF expression over time.