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
Source: PubMed


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.

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    • "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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    • "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.
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    • "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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