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

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The paper developed a continuum diffusion, finite-element model in COMSOL to describe drug transport through porous polymeric intravitreal microcapsules, using cylindrical capsules with either a single PCL layer or a bi-layered chitosan–PCL structure. Using published release data, it estimated transport parameters (including porosity, tortuosity, and mass transfer rates) and showed that the model reproduced experimental release profiles for two capsule sizes, three salt leaching concentrations, and two model drugs (bovine serum albumin and bevacizumab), while acknowledging the reliance on published release datasets for parameter fitting. Design exploration indicated polymer thickness was the dominant factor for release, and adding a chitosan layer reduced initial burst and prolonged delivery. Relevance to endometriosis: the paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

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.
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Abstract 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. Full Text Availability The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.

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