Compartmental and COMSOL Multiphysics 3D Modeling of Drug Diffusion to the Vitreous Following the Administration of a Sustained-Release Drug Delivery System

Emily Dosmar; Gabrielle Vuotto; Xingqi Su; Emily Roberts; Abigail Lannoy; Garet J Bailey; William F Mieler; Jennifer J Kang-Mieler

doi:10.3390/pharmaceutics13111862

Compartmental and COMSOL Multiphysics 3D Modeling of Drug Diffusion to the Vitreous Following the Administration of a Sustained-Release Drug Delivery System

Pharmaceutics. 2021 Nov 4;13(11):1862. doi: 10.3390/pharmaceutics13111862.

Authors

Emily Dosmar¹, Gabrielle Vuotto¹, Xingqi Su¹, Emily Roberts¹, Abigail Lannoy¹, Garet J Bailey¹, William F Mieler², Jennifer J Kang-Mieler³

Affiliations

¹ Department of Biology and Biomedical Engineering, Rose-Hulman Institute of Technology, 5500 Wabash Avenue, Terre Haute, IN 47803, USA.
² Department of Biomedical Engineering, Illinois Institute of Technology, 10 W 35th St., Chicago, IL 60616, USA.
³ Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1200 W Harrison St., Chicago, IL 60607, USA.

Abstract

The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery system (DDS) using a computational model and a 3D model of the eye. Hydrogel DDSs loaded with vancomycin (VAN) were synthesized and release behavior was characterized in vitro. Four different compartmental and four COMSOL models of the eye were developed to describe transport into the vitreous originating from a DDS placed topically, in the subconjunctiva, subretinally, and intravitreally. The concentration of the simulated DDS was assumed to be the initial concentration of the hydrogel DDS. The simulation was executed over 1500 and 100 h for the compartmental and COMSOL models, respectively. Based on the MATLAB model, topical, subconjunctival, subretinal and vitreous administration took most (~500 h to least (0 h) amount of time to reach peak concentrations in the vitreous, respectively. All routes successfully achieved therapeutic levels of drug (0.007 mg/mL) in the vitreous. These models predict the relative build-up of drug in the vitreous following DDS administration in four different points of origin in the eye. Our model may eventually be used to explore the minimum loading dose of drug required in our DDS leading to reduced drug use and waste.

Keywords: COMSOL 3D modeling; compartmental modeling; hydrogels; intravitreal delivery; ocular drug delivery; pharmacokinetic modeling; subconjunctival delivery; subretinal delivery; targeted drug delivery; topical delivery.