Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel.
ABSTRACT 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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ABSTRACT: To investigate the potential of nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with l-phenylalanine (γ-PGA-Phe NPs) for the treatment of retinal diseases, γ-PGA-Phe NPs (200nm) were tested with macrophages and microglia in vitro or by intravitreal administration into normal or pathological rat eyes. The anti-inflammatory effects of the NPs containing dexamethasone (DEX-NPs) were examined using qRT-PCR in vitro by counting activated microglia and Fluorogold-labeled retinal ganglion cells in the retinas under excitotoxicity or by counting TUNEL (+) photoreceptors in the detached retinas. The NPs were taken up efficiently by cultured macrophages or microglia. At day 7, 60-80% of the diffuse signal remained in the cytoplasm of these cells. In normal rat eyes, the NPs did not accumulate in the retinas and no inflammatory cells were recruited. Conversely, under pathological conditions, the NPs were localized in activated CD11b-positive cells in the retina. DEX-NPs suppressed the expression of TNFα and MCP-1 in cultured macrophages or microglia, the activation of microglia, the loss of retinal ganglion cells (RGCs) in excitotoxic retinas, and the number of TUNEL (+) photoreceptors in detached retinas. These data suggest that γ-PGA-Phe NPs can be a powerful tool for suppressing inflammatory cells in pathological conditions in the retina.Journal of Controlled Release 12/2010; 151(1):65-73. · 7.63 Impact Factor
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ABSTRACT: Abstract Purpose: To evaluate the toxicokinetics and tolerability (local ocular and general toxicity) of the anti-inflammatory agent, dexamethasone phosphate (a prodrug of dexamethasone) delivered to the eye in rabbits by transscleral iontophoresis. Methods: Female rabbits (n=6/group) received dexamethasone phosphate (40 mg/mL ophthalmic solution, EGP-437) transsclerally to the right eye (OD) using the Eyegate(®) II ocular iontophoresis delivery system once biweekly for 24 consecutive weeks at current doses of 10, 14, and 20 mA-min and current levels up to, and including -4 mA for 3.5-5 min. The study included 2 control groups (n=6/group): (1) a noniontophoresis control [an ocular applicator-loaded citrate buffer (placebo) without current] and (2) an iontophoresis control (a citrate buffer plus cathode iontophoresis at 20 mA-min, -4 mA for 5 min). Recoverability was evaluated 4 weeks following the last dose in 2 animals per group. The left eye (OS) was untreated and served as an internal control for each animal. Ocular and general safety of dexamethasone phosphate and dexamethasone were assessed. Other evaluations included toxicokinetics, ophthalmic examinations, intraocular pressure (IOP) measurements, electroretinographs, clinical observations, body weight, hematology and serum chemistry, gross necropsy, organ weight, and microscopic histopathology. Results: The biweekly transscleral iontophoresis with either the citrate buffer or dexamethasone phosphate at cathodic doses up to, and including 20 mA-min and currents up to, and including -4 mA for 24 weeks was well-tolerated. Transient signs of conjunctival hyperemia and chemosis, mild corneal opacity, and fluorescein staining of the cornea were noted and attributed to expected ocular reactions to the temporary placement of the ocular applicator and application of iontophoresis. There were no dexamethasone phosphate-, dexamethasone-, or iontophoresis-related effects on IOP, electroretinography, or histopathology. Reductions in body weight gain, anemia, decreased leukocyte and lymphocyte counts, compromised liver function, enlarged liver, and reduced spleen weight were consistent with systemic corticosteroid-mediated pharmacology, repeated use of anesthesia, stress, and sedentariness, and unlikely to be related to iontophoresis application. Conclusions: The results of this investigation suggest that repeated transscleral iontophoresis with dexamethasone phosphate may be safe for use as a treatment for inflammatory ocular disorders that require prolonged and/or repeated corticosteroid therapy.Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 07/2013; · 1.46 Impact Factor
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ABSTRACT: The basic concepts, major mechanisms, technological developments and advantages of the topical application of lipid-based systems (microemulsions, nanoemulsions, liposomes and solid lipid nanoparticles), polymeric systems (hydrogels, contact lenses, polymeric nanoparticles and dendrimers) and physical methods (iontophoresis and sonophoresis) will be reviewed. Although very convenient for patients, topical administration of conventional drug formulations for the treatment of eye diseases requires high drug doses, frequent administration and rarely provides high drug bioavailability. Thus, strategies to improve the efficacy of topical treatments have been extensively investigated. In general, the majority of the successful delivery systems are present on the ocular surface over an extended period of time, and these systems typically improve drug bioavailability in the anterior chamber whereas the physical methods facilitate drug penetration over a very short period of time through ocular barriers, such as the cornea and sclera. Although in the early stages, the combination of these delivery systems with physical methods would appear to be a promising tool to decrease the dose and frequency of administration; thereby, patient compliance and treatment efficacy will be improved.The Journal of pharmacy and pharmacology. 04/2014; 66(4):507-30.