Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. Journal of Controlled Release
(Impact Factor: 7.71).
10/2005; 106(3):386-90. DOI: 10.1016/j.jconrel.2005.05.020
To evaluate dexamethasone penetration to the eye after a short transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic device.
Iontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with a current intensity of 1 mA for 1 and 4 min. Transconjunctival and transscleral iontophoresis were performed twice for 2 min at two near places in the pars-plana area, on the conjunctival membrane or directly on the sclera. Dexamethasone concentrations were assayed using HPLC.
Dexamethasone levels in the rabbit cornea after a single transcorneal iontophoresis for 1 min were up to 30 fold higher compared to those obtained after frequent eye drop instillation. Also, high drug concentrations were obtained in the retina and sclera 4 h after transscleral iontophoresis.
A short low current non-invasive iontophoretic treatment using dexamethasone-loaded hydrogels has potential clinical value in increasing drug penetration to the anterior and posterior segments of the eye.
Available from: Masoud Soheilian
- "Eljarrat-Binstock et al49 achieved therapeutic dexamethasone levels in different eye segments using a lower current density (5.1mA/cm2) for only 4 minutes. "
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ABSTRACT: Corticosteroids have been the mainstay of uveitis therapy. When intraocular inflammation is unresponsive to steroids, or steroid related side effects become a concern, steroid-sparing medications may be administered which can be classified into immunosuppressive and immunomodulatory agents. Uveitis treatment can be delivered systemically, topically, periocularly or intraocularly. All of the above mentioned medications can entail significant systemic side effects, particularly if administered for prolonged durations, which may become treatment-limiting. Some medications, particularly hydrophobic compounds, may poorly cross the blood-retinal barrier. Topical medications, which have the least side effects, do not penetrate well into the posterior segment and are unsuitable for posterior uveitis which is often sight-threatening. Intraocular or periocular injections can deliver relatively high doses of drug to the eye with few or no systemic side effects. However, such injections are associated with significant complications and must often be repeated at regular intervals. Compliance with any form of regular medication can be a problem, particularly if its administration is associated with discomfort or if side effects are unpleasant. To overcome the above-mentioned limitations, an increasing number of sustained-release drug delivery devices using different mechanisms and containing a variety of agents have been developed to treat uveitis. This review discusses various current and future sustained-release ophthalmic drug delivery systems for treatment of uveitis.
Available from: Linhua Zhang
- "It has proved to be effective to treat inflammation after cataract surgery, decreasing the risk of systemic toxicity and ocular side effects.20 Other ocular drug delivery systems currently under investigation for DEX include intraocular lens containing a DEX drug delivery system (IOL-DDS),19 an iontophoretic device assembled with DEX-loaded hydrogels17 and DEX nanoparticles.21 "
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ABSTRACT: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid-co-glycolic acid) nanoparticles (DEX-NPs) in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L(-1). Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.
Available from: Eun-Kee Jeong
- "Results from previous transscleral iontophoresis studies are generally consistent with this trend. For example, iontophoresis studies of dexamethasone phosphate, methylprednisolone, amikacin, cefazolin, ticarcillin, and gentamicin showed an increase in delivery into the eye when the electric current of iontophoresis was increased (Barza et al., 1986;Behar-Cohen et al., 2002;Vollmer et al., 2002;Eljarrat-Binstock et al., 2005). In a study of the effects of current density upon iontophoretic delivery of fluorescein into the posterior segment of the eye, electric current density was shown to significantly affect transscleral delivery when the current density was above 40 mA/cm 2 (Maurice, 1986). "
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ABSTRACT: 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 4mA (current density 10 and 20mA/cm(2)) and 20-60min, 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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