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

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.

Smart molecules in ophthalmology: Hydrogels as responsive systems for ophthalmic applications

“…nonbiodegradable and biocompatible) were also engineered for the controlled intravitreal release of vancomycin using a polyNIPAAm hydrogel crosslinked with the PEG-DA polymer. [118] However, drug kinetic remains to be improved: intravitreal administration of vancomycin-loaded PEG-based hydrogel resulted in a rapid peak in its -19 of 30 concentration in comparison to the topically administered drug, in detriment of a sustainable drug concentration over time. [118] A major challenge for the clinical translation of PEGbased thermoresponsive hydrogels resides in their prolonged gelation times.…”

“…[118] However, drug kinetic remains to be improved: intravitreal administration of vancomycin-loaded PEG-based hydrogel resulted in a rapid peak in its -19 of 30 concentration in comparison to the topically administered drug, in detriment of a sustainable drug concentration over time. [118] A major challenge for the clinical translation of PEGbased thermoresponsive hydrogels resides in their prolonged gelation times. [119] To leverage this drawback, using Diels-Alder reactions, Gregoritza et al engineered two in situ forming four-armed and eight-armed thermoresponsive Poloxamine hydrogels with optimal LCST.…”

“…Furthermore, variability in physicochemical properties within thermoresponsive hydrogels was shown to be dependent on hydrogel modification with polymers. [118] Therefore, a balance between degradability and efficacity must be considered for reaching optimal and sustainable drug concentrations. It is evident that further studies are required to explore the long-term efficacy, safety, biocomposition and biocompatibility of smart hydrogels for intravitreal and suprachoroidal injections.…”

“…Given the complexity of the human eye, these results cannot be fully generalized. Furthermore, variability in physicochemical properties within thermoresponsive hydrogels was shown to be dependent on hydrogel modification with polymers [118] . Therefore, a balance between degradability and efficacity must be considered for reaching optimal and sustainable drug concentrations.…”

Biomembrane-Based Nanostructure- and Microstructure-Loaded Hydrogels for Promoting Chronic Wound Healing

“… 74 Nanostructures and microstructures can be released from hydrogels when exposed to certain stimuli, such as temperature, pH, enzymes and magnetic fields. 75 , 76 …”