Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to encapsulate ranibizumab in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs) for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy.