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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish
Article number1862
JournalPharmaceutics
Volume13
Issue number11
DOIs
StatePublished - Nov 2021

Keywords

  • COMSOL 3D modeling
  • Compartmental modeling
  • Hydrogels
  • Intravitreal delivery
  • Ocular drug delivery
  • Pharmacokinetic modeling
  • Subconjunctival delivery
  • Subretinal delivery
  • Targeted drug delivery
  • Topical delivery

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