The Investigation of Multifunctional Microbubbles for Sustained Release in Intravitreal Injection of anti-VEGF agents.  (Xu, Letson, Roberts) The goal of this ongoing project is to investigate novel methods of encapsulation of anti-VEGF agents in the fabrication of microbubbles for sustained delivery via intravitreal injection in the treatment of age-related macular degeneration. Current double-emulsion encapsulation methods are detrimental to the bioactivity of Lucentis. It is proposed that the new methodology under study will not substantially reduce bioactivity with sustained delivery. In addition, we have shown that freeze-drying of Lucentis also does not substantially alter bioactivity, which allows reconstitution at a much higher concentration for encapsulation in microbubbles. In addition to the anti-VEGF agents, fluorescent compounds can be encapsulated simultaneously to allow visualization of the microbubbles in the vitreous chamber to monitor rate of delivery of anti-VEGF therapy. Note that the Doctoral Student in Biomedical Engineering working on this project is also our Ohio Lions Eye Research Fellow. We received a substantial amount of Lucentis from Genentech in support of our research, and this work was presented at ARVO this year. Manuscripts are in preparation.

“Targeted delivery of biodegradable multifunctional nanoparticles, conjugated with Lucentis, for integrated imaging and therapy of age-related macular degeneration.” GenenTech Reagent grant, PI: Ronald Xu, Co-I’s: Cynthia Roberts, Alan Letson, $80,000 worth of Lucentis™ anti-VEGF antibody.

Leilei Zhang, Jeff Xu, Jiwei Huang, Cynthia Roberts, Ronald Xu. 2010. Bevacizumab (Avastin) conjugated microbubbles for anti-VEGF treatment of neovascular age-related macular degeneration. In: Proc. SPIE: 7550-61.

Leilei Zhang, Cynthia J Roberts, Alan D Letson, Ronald Xu. “Comparison of Avastin and Lucentis conjugated microbubbles for targeted delivery in age-related macular degeneration. ARVO E-Abstract 477.