A Study of Drug Transport in the Vitreous Humor: Effect of Drug Size; Comparing Micro- and Macro-scale diffusion; Assessing Vitreous Models; and Obtaining In Vivo Data

• Main Author: Gajraj, Rhiad
• Other Authors: Cheng, Yu-Ling
• Language: en_ca
• Published: 2012
• Subjects: vitreous humor; diffusion; drug; DOSY NMR; vitreous; DOSY; fluorotron; fluorophotometry; spectralis; diffusivity; 0542
• Online Access: http://hdl.handle.net/1807/33202

Treatment of vision impairing diseases involves drug transport through the vitreous humor. Diffusion cells were used to measure macro-scale (mutual) diffusivity (Dm) to understand how solute size affects diffusion through the vitreous humor of rabbit and porcine eyes. Solutes examined included timolol maleate, dexamethasone sodium phosphate (DMSP), sodium fluorescein, and FITC-dextrans (4, 40, and 150kDa). Diffusivity was inversely dependent on solute size. The Dm's of small solutes in the vitreous were 30 – 65% of that in PBS, while the Dm's of large solutes were 40 – 60% of that in PBS. Extrapolations to the human eye produced similar results using diffusivities based on either species. We used Diffusion Ordered NMR Spectroscopy to measure micro-scale (self) diffusivity (Ds) of DMSP through vitreous humor. The Ds and Dm were significantly different in PBS, but similar in vitreous. A method for obtaining in vivo imagery and data of vitreous fluorophore distribution is also presented.