Diffusive Transport in the Vitreous Humor: Experimental and Analytical Studies

Abstract

In relation to intravitreal drug delivery, predictive mathematical models for drug transport are being developed, and to effectively implement these for retinal delivery, the information on biophysical properties of various ocular tissues is fundamentally important. It is therefore necessary to accurately measure the diffusion coefficient of drugs and drug surrogates in the vitreous humor. In this review, we present the studies conducted by various researchers on such measurements over the last several decades. These include imaging techniques (fluorescence and magnetic resonance imaging (MRI)) that make use of introducing a contrast agent or a labeled drug into the vitreous and tracking its diffusive movement at various time points. A predictive model for the same initial conditions when matched with the experimental measurements provides the diffusion coefficient, leading to results for various molecules ranging in size from approximately 0.1 to 160 kDa. For real drugs, the effectiveness of this system depends on the successful labeling of the drugs with suitable contrast agents such as fluorescein and gadolinium or manganese so that fluorescence or MR imagining could be conducted. Besides this technique, some work has been carried out using the diffusion apparatus for measuring permeation of a drug across an excised vitreous body from a donor chamber to the receptor by sampling assays from the chambers at various time intervals. This has the advantage of not requiring labeling but is otherwise more disruptive to the vitreous. Some success with nanoparticles has been achieved using dynamic light scattering (DLS), and presently, radioactive labeling is being explored.

Mathematical Model of Macromolecular Drug Transport in a Partially Liquefied Vitreous Humor

“…There have been several recent studies on the measurement of the diffusion coefficient of large molecules in the vitreous humor (see Penkova et al [33], Rattanakijsuntorn et al [34], Zhang et al [35]). Also, a catalog of diffusion coefficient values has been provided in the review by Penkova [36]. For the inlet velocity of 0.000147 mm/s, the two chosen diffusion coefficients values represent P eclet numbers 2:652 Â 10 5 and 4:42 Â 10 2 .…”

Experimental and mathematical approaches for drug delivery for the treatment of wet age-related macular degeneration

“…Ocular pharmacokinetics (PK) models aim to describe the dynamics of drug concentration in the eye by incorporating the absorption, distribution, metabolism, and excretion of a drug into the models [ 143 ]. For these models to be effectively implemented in the eye, information on the biophysical properties of the involved ocular tissues is important [ 144 ]. Experimental and analytical studies have been conducted to accurately measure diffusion coefficients of drugs and drugs surrogates, as well as hydraulic resistance, in the different ocular tissues [ 145 - 151 ].…”

Measurement of the Hydraulic Conductivity of the Vitreous Humor

“…al., 2014;Rattanakijsuntorn et. al, 2018) and more recently, a comprehensive review of in various studies on this subject have been provided (Penkova et. al, 2019).…”