In silico model of bevacizumab sustained release from intravitreal administrated PLGA drug-loaded microspheres

Abstract

This paper demonstrates a computational model of the bevacizumab release from intravitreal administrated microspheres made of biodegradable poly(lactic-co-glycolic acid) PLGA. Intravitreal administrated bevacizumab is known to be an efficient antibody directed against VEGF expression supplied in the age-related macular degeneration (AMD) therapy. The developed diffusion-convection model of the ocular drug transport considering bevacizumab controlled release from intravitreal injected degradable PLGA microspheres and the drug clearance caused by the aqueous humor drainage. The applied model of the drug release from biodegradable microspheres was based on the Koizumi empirical approach. The aqueous humor drainage was predicted by computer fluid dynamics (CFD). The developed model enables for prediction of the time-drug concentration profiles separately for the vitreous and the aqueous body. It was validated against the experimental rabbit models data on the bevacizumab controlled release from intravitreal injected PLGA nano- and microspheres. One can see that the numerical results are in good agreement with the experimental results obtained for PLGA drug-loaded spheres having micrometer size. It is expected that the developed model of drug sustained release and ocular transport will allow for reliable evaluation of planned anti-VEGF therapies.