title: Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging.
abstract: Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist) released from a polymer-based implant in rabbit vitreous using T1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm2 s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroidsclera membrane) of 6.0 x 10(-8) cm2 s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.
authors.affiliation: Division of Bioengineering and Physical Science ORS, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Kim
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lizak
authors.forename: Ginger
authors.initials: G
authors.lastname: Tansey
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Michael R
authors.initials: MR
authors.lastname: Robinson
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Nam Sun
authors.initials: NS
authors.lastname: Wang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lutz
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003287:Contrast Media; D004343:Drug Implants; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D005123:Eye / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019786:Gadolinium DTPA / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011817:Rabbits; D014018:Tissue Distribution; D014822:Vitreous Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D003287:Contrast Media; D004343:Drug Implants; D019786:Gadolinium DTPA