Hindered convective transport of nanoparticles and macromolecules in the vitreous humor

Abstract

Purpose: 1. To investigate the extent of transport enhancement of macromolecules and nanoparticles due to convective flow of water in the vitreous humor. 2. To establish deviation from convective transport predictions by forced-flow experiments and comparison with conventional theory calculations. 3. To propose corrections to convective transport to allow for large-particle hindrance in the vitreous humor.

Methods: Fresh ex vivo whole bovine eyes were individually injected with two gadolinium-based contrast agents [Gd-Albumin, and 30 nm gadolinium-based particles (Gado CELLTrackTM, Biopal, Worcester, MA)]. After imaging the eye, the contrast-agent bolus was subjected to a high rate of water flow with a syringe pump. The water (0.9% saline solution) was injected at the top of the bovine eye at 100 μl/min, and was allowed to drain through small slits cut at the bottom of the eyeball. After one hour of pumping, the eye was imaged again and the contrast-agent distribution was obtained. For theoretical comparison the convective transport was also evaluated by numerical modeling based on the conventional convection-diffusion equation.

Results: The experimentally measured convective transport of Gd-Albumin and 30 nm nanoparticles was found to be somewhat slower than the carrier (0.9% saline solution). The conventional convection-diffusion equation with the u.▽c term for convective transport seems to over-predict the convection rate, indicating some degree of hindrance to convection for nanoparticles and Gd-Albumin.

Conclusions: It has been claimed in several theoretically-based investigations that convection significantly enhances the transport of large particles and macromolecules in the vitreous humor. However, current investigations have raised questions about the validity of using the unhindered convective term u.▽c which does not discriminate between the different solutes. We have hypothesized that large molecules, when subjected to high rate of water flow in the vitreous humor, will experience resistance, depending on the respective permeabilities of the injected surrogate solute. We are proposing that the usual convection term be adjusted to allow for the filtration effect on the larger particles in the form (1-σ)u.▽c with important implications for computational modeling.

Keywords: 763 vitreous • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 608 nanomedicine