Controlled Drug Release from an Ocular Implant: An Evaluation Using Dynamic Three-Dimensional Magnetic Resonance Imaging

Kim, Hyuncheol; Robinson, Michael R.; Lizak, Martin J.; Tansey, Ginger; Lutz, Robert J.; Yuan, Peng; Wang, Nam S.; Csaky, Karl G.

doi:10.1167/iovs.04-0091

Cited by 117 publications

(83 citation statements)

References 38 publications

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“…Dynamic barriers are active in vivo but cease postmortem, while static barriers are always present. A comparison of scans acquired in vivo and postmortem revealed increased penetration of a magnetic resonance imaging tracer released from a polymeric episcleral implant into the anterior chamber and vitreous postmortem but not in vivo [122] . Similar results were obtained after subconjunctival injection of manganese ions [123] .…”

Section: Discussionmentioning

confidence: 95%

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

et al. 2007

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Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases. Transscleral drug delivery systems require drugs to permeate through several layers of ocular tissue (sclera, Bruch’s membrane-choroid, retinal pigment epithelium) to reach the neuroretina. As a result, a steep drug concentration gradient from the sclera to the retina is established, and very low concentrations of drug are detected in the retina. This steep gradient is created by the barriers to transport that hinder drug molecules from successfully reaching the retina. A review of the literature reveals 3 types of barriers hindering transscleral drug delivery: static, dynamic and metabolic. While static barriers have been examined in detail, the literature on dynamic and metabolic barriers is lacking. These barriers must be investigated further to gain a more complete understanding of the transport barriers involved in transscleral drug delivery.

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Section: Discussionmentioning

confidence: 95%

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

et al. 2007

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“…5). Kim et al (2004) reported that transscleral delivery of gadolinium-diethylenetriaminepentaacetic acid to the vitreous in rabbits was approximately 30-fold higher after euthanasia because of the impairment of dynamic barriers, which include blood and lymphatic clearance pathways. These authors also showed that under in vivo conditions, the elimination rate constant from the subconjunctival space into episcleral veins and conjunctival lymphatics was 3 log units higher than the transport rate constant into the vitreous.…”

Section: Thakur Et Almentioning

confidence: 99%

Influence of Drug Solubility and Lipophilicity on Transscleral Retinal Delivery of Six Corticosteroids

Thakur

Kadam²,

Kompella³

2011

Drug Metab Dispos

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ABSTRACT:The influence of drug properties including solubility, lipophilicity, tissue partition coefficients, and in vitro transscleral permeability on ex vivo and in vivo transscleral delivery from corticosteroid suspensions was determined. Solubility, tissue/buffer partition coefficients for bovine sclera and choroid-retinal pigment epithelium (CRPE), and in vitro bovine sclera and sclera-choroid-retinal pigment epithelium (SCRPE) transscleral transport were determined at pH 7.4 for triamcinolone, prednisolone, dexamethasone, fluocinolone acetonide, triamcinolone acetonide, and budesonide in solution. Ex vivo and in vivo transscleral delivery was assessed in Brown Norway rats after posterior subconjunctival injection of a 1 mg/ml suspension of each corticosteroid. Corticosteroid solubility and partition coefficients ranged from ϳ17 to 300 g/ml and 3.0 to 11.4 for sclera and from 7.1 to 35.8 for CRPE, respectively, with the more lipophilic molecules partitioning more into both tissues.

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“…Particularly, blood vasculature clearance is a major barrier in transscleral transport (Li et al, 2004b). Conjunctival lymphatic clearance and other factors (Kim et al, 2004) also contribute to the transscleral barrier. The similarity of the results of transscleral iontophoresis in vivo and subconjunctival injection postmortem suggests that the applied electric field can potentially drive the permeants across the barrier due to clearance such as the blood vasculature barrier to enhance drug delivery.…”

Section: Transscleral Iontophoresismentioning

confidence: 99%

“…Studies employing MRI to follow ocular drug delivery in rabbits have been reported (Li et al, 2004a,b;Kim et al, 2004). An aim of the earlier experiments was to assess MRI as a technique to study ocular delivery and pharmacokinetics in an animal model (Li et al, 2004a,b).…”

Section: Introductionmentioning

confidence: 99%

Examination of penetration routes and distribution of ionic permeants during and after transscleral iontophoresis with magnetic resonance imaging

Molokhia

Jeong

Higuchi

et al. 2007

International Journal of Pharmaceutics

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Previously, transscleral and transcorneal iontophoretic delivery was studied and compared to passive delivery and intravitreal injection using nuclear magnetic resonance imaging (MRI). The objective of the present study was to employ MRI to further investigate the factors affecting transscleral iontophoretic delivery. In the present study, anodal and cathodal constant current transscleral iontophoresis were conducted with excised sclera in side-by-side diffusion cells in vitro and with rabbits in vivo. The total current and duration of application were 2 and 4 mA (current density 10 and 20 mA/cm 2 ) and 20-60 min, respectively. The delivery and distribution of the model permeants manganese ion (Mn 2+ ) and manganese ethylenediaminetetraacetic acid complex (MnEDTA 2− ) into the eye during iontophoresis were determined with MRI and compared with the results obtained in previous studies of subconjunctival injection and passive delivery. Both anodal and cathodal iontophoresis provided significant enhancement in ocular delivery compared to passive transport in the in vitro and in vivo experiments. Transscleral iontophoretic delivery was related to the position and duration of the iontophoresis application in vivo. Permeants were observed to be delivered primarily into the anterior segment of the eye when the pars plana was the application site. Extending the duration of iontophoresis at this site allowed the permeants to be delivered into the vitreous more deeply and to a greater extent than when the application site was at the back of the eye near the fornix. The present results show that electrode placement was an important factor in transscleral iontophoresis, and the ciliary body (pars plana) was determined to be the pathway of least resistance for iontophoretic transport. These new findings continue to support the utility of MRI as a noninvasive technique in ocular drug delivery research and testing.

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Controlled Drug Release from an Ocular Implant: An Evaluation Using Dynamic Three-Dimensional Magnetic Resonance Imaging

Cited by 117 publications

References 38 publications

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

Influence of Drug Solubility and Lipophilicity on Transscleral Retinal Delivery of Six Corticosteroids

Examination of penetration routes and distribution of ionic permeants during and after transscleral iontophoresis with magnetic resonance imaging

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