Assessment of Subconjunctival Delivery with Model Ionic Permeants and Magnetic Resonance Imaging

Li, S. Kevin; Molokhia, Sarah; Jeong, Eun Kee

doi:10.1007/s11095-004-7669-3

Cited by 38 publications

(55 citation statements)

References 24 publications

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“…(1). Passive transscleral permeation of Mn 2+ and MnEDTA 2− was determined in a previous study, and the permeability coefficients were 3.5 × 10 −5 and 2.5 × 10 −5 cm/s, respectively (Li et al, 2004b). These passive permeability coefficients are significantly lower than those of iontophoresis in the present study.…”

Section: In Vitro Resultscontrasting

confidence: 49%

“…At high donor concentrations such as 40 mM Mn 2+ and 0.1 M MnEDTA 2− , the permeability coefficients were significantly lower than those at lower concentrations. The results in previous passive permeation studies in vitro suggested minimal interference from the counterions and little effects due to the different ionic strength in the donor and receiver upon transport across the sclera (Li et al, 2004b). However, during transscleral iontophoresis, the present results suggest counterion influence upon transport under an electric field.…”

Section: In Vitro Resultssupporting

confidence: 46%

“…Transscleral iontophoresis was shown to enhance the penetration of the permeant into the anterior chamber and into the posterior chamber near the ciliary body directly under the electrode/conjunctiva interface. In contrast to iontophoresis, subconjunctival injections (Li et al, 2004b) and passive diffusion (Li et al, 2004a) did not deliver a significant amount of the probe ions into the eye in vivo. The effects of the electric field upon drug delivery into the eye over passive diffusion are clearly demonstrated.…”

Section: Transscleral Iontophoresismentioning

confidence: 79%

“…A two-chamber side-by-side diffusion cell system with excised rabbit sclera was used in the experiments (Li et al, 2004b(Li et al, ,2005. Each compartment of the diffusion cell has a 2-ml volume and an effective diffusional area of around 0.2 cm 2 .…”

Section: In Vitro Transport Experimentsmentioning

confidence: 99%

“…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). In one study, it was found that passive transport of Mn 2+ and of MnEDTA 2− into the eye after subconjunctival injection could not be detected by MRI over a 2-h period after injection in vivo (Li et al, 2004b). However, when the animals were sacrificed before subconjunctival injection in a postmortem experiment, significant penetration of Mn 2+ and MnEDTA 2− into the ciliary body, anterior chamber, and posterior chamber near the injection site was observed after the injection, suggesting the importance of clearance and the blood vasculature barrier in the subconjunctival route.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: In Vitro Resultscontrasting

confidence: 49%

Section: In Vitro Resultssupporting

confidence: 46%

Section: Transscleral Iontophoresismentioning

confidence: 79%

Section: In Vitro Transport Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Influence of Asymmetric Donor–Receiver ion Concentration Upon Transscleral Iontophoretic Transport

Zhang

Zhu

et al. 2005

Journal of Pharmaceutical Sciences

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Examination of Barriers and Barrier Alteration in Transscleral Iontophoresis

Molokhia

Jeong

Higuchi

et al. 2008

Journal of Pharmaceutical Sciences

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The flux enhancing mechanisms of transscleral iontophoresis are not well understood. The objective of the present study was to investigate the ocular barrier and barrier alterations in transscleral iontophoretic delivery with magnetic resonance imaging (MRI). Experiments involving constant current transscleral iontophoresis of 2 mA (current density 10 mA/cm(2)) and subconjunctival injection were conducted with rabbits in vivo and postmortem and with excised sclera in side-by-side diffusion cells in vitro. The postmortem and in vitro experiments were expected to be helpful in clarifying the importance of vascular clearance and other transport barriers in transscleral iontophoresis. Manganese ion (Mn(2+)) and manganese ethylenediaminetetraacetic acid complex (MnEDTA(2-)) were the model permeants. The results show that pretreatment of the eye with an electric field by iontophoresis enhanced subconjunctival delivery of the permeants to the anterior segment of the eye in vivo. This suggests that electric field-induced barrier alterations can be an important absorption enhancing mechanism of ocular iontophoresis. Penetration enhancement was magnified in the postmortem experiments with larger amounts of the permeants delivered into the eye and to the back of the eye. The different results observed in the in vivo and postmortem studies can be attributed to ocular clearance in ocular delivery.

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Assessment of Subconjunctival Delivery with Model Ionic Permeants and Magnetic Resonance Imaging

Cited by 38 publications

References 24 publications

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

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

Influence of Asymmetric Donor–Receiver ion Concentration Upon Transscleral Iontophoretic Transport

Examination of Barriers and Barrier Alteration in Transscleral Iontophoresis

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