Modeling and Design of Multi-layered Cylindrical Microcapsules for Intravitreal Controlled Release.

Chronic diseases often require repeated oral or local administration, which can compromise patient compliance. In wet age-related macular degeneration (AMD), current therapies rely on intravitreal injections of anti-vascular endothelial growth factor agents every four to six weeks to maintain therapeutic drug levels. Controlled-release drug delivery systems offer a promising alternative by reducing injection frequency and extending drug release. In this study, we developed a continuum diffusion model to describe drug transport through porous polymeric microcapsules, implemented using the finite element method in COMSOL Multiphysics. The case study focused on cylindrical microcapsules fabricated with either a single polycaprolactone (PCL) layer or a bi-layered chitosan-PCL structure, tested at two capsule sizes and three salt leaching concentrations. Bovine serum albumin and bevacizumab were used as model drugs. Parameter estimation was performed using published release data, with a progressive fitting strategy that carried forward parameters from simpler systems into more complex designs. The model reproduced experimental release profiles across formulations and identified key transport parameters governing release dynamics, including porosity, tortuosity, and mass transfer rates. Design exploration revealed that polymer thickness was the dominant factor controlling release, while addition of the chitosan layer moderated the initial burst and extended therapeutic delivery. This framework demonstrates how computational modeling can reduce experimental burden, guide design optimization, and support the development of long-acting intravitreal drug delivery systems to treat wet AMD by linking drug release kinetics to design variables.