Evaluation of Ocular and General Safety Following Repeated Dosing of Dexamethasone Phosphate Delivered by Transscleral Iontophoresis in Rabbits

Patane, Michael A.; Schubert, William; Sanford, Thomas; Gee, Raymond; Burgos, Melissa; Isom, William P.; Ruiz-Pérez, Begoña

doi:10.1089/jop.2012.0175

Cited by 25 publications

(13 citation statements)

References 16 publications

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“…Although only the 25% DSP group showed statistically significant reduction in body weight, the consistent decline in body weights of the animals in these two groups indicate that long-term exposure at these levels of DSP-Visulex dosing (i.e., 15 and 25% DSP for 20 minutes) may have significant systemic side effects on rabbit. Since all animals exhibited systemic exposure of both DSP and DEX after single administration of the DSP-Visulex (discussed above), this is an expected outcome after multiple treatments of DSP-Visulex for 3 months [42,43]. It should be noted that the 20-minute treatment duration and 25% DSP tested in this study were an exaggerated wearing time and concentration to find the adverse effect (if any).…”

Section: Ocular Toxicity Of Dsp-visulex In Animalmentioning

confidence: 68%

A Novel Ocular Drug Delivery System of Dexamethasone Sodium Phosphate for Noninfectious Uveitis Treatment

Papangkorn¹,

Higuchi²,

Brar³

et al. 2019

Advances in the Diagnosis and Management of Uveitis

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Treatment of anterior uveitis commonly requires 6-8 times daily administration of eye drops, which often leads to poor patient compliance. The treatment of intermediate and posterior uveitis is restricted to either oral medications with significant systemic side effects or local invasive methods, which are more expensive and associated with the development of ocular complications. There is an unmet need for a new drug delivery system that addresses these challenges. DSP-Visulex is a noninvasive drug delivery system that administers dexamethasone sodium phosphate by passive diffusion through the limbal sclera into the interior of the eye utilizing the transscleral pathway. Once-a-week administration of DSP-Visulex treatment regimens (i.e., 1-5 doses per month) has shown to be safe and efficacious for noninfectious uveitis in animal models including anterior uveitis, posterior uveitis, and/ or panuveitis. In a clinical study of anterior uveitis, the DSP-Visulex treatments also have been shown to be safe and well tolerated and their efficacy (administered on days 1, 3, 8, and 15 with an optional treatment on Day 22) was comparable to that of the daily prednisolone acetate drops.

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Section: Ocular Toxicity Of Dsp-visulex In Animalmentioning

confidence: 68%

A Novel Ocular Drug Delivery System of Dexamethasone Sodium Phosphate for Noninfectious Uveitis Treatment

Papangkorn¹,

Higuchi²,

Brar³

et al. 2019

Advances in the Diagnosis and Management of Uveitis

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“…Iontophoresis is a well‐known drug‐delivery strategy and has been used in ophthalmology for decades . It consists in transferring charged molecules to a target tissue through the application of a low‐intensity electric field and has been shown to be safe both in ex vivo and in vivo studies . Current densities up to 4.0 mA/cm 2 for 10 min through the sclera of rabbits have been shown to cause no alterations to eye function or structure .…”

Section: Discussionmentioning

confidence: 99%

Assessment of trans‐scleral iontophoresis delivery of lutein to the human retina

Lombardo

Villari

Micali

et al. 2017

Journal of Biophotonics

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The efficacy of novel scleral iontophoresis device for in situ delivery of lutein to the human retina was assessed by Resonance Raman spectroscopy (RRS) technique. Eight human donor eye globes were used for experiments, 6 of which underwent trans-scleral iontophoresis delivery of lutein and the other 2 were used as controls. The scleral iontophoresis applicator was filled with liposome-enriched 0.1% lutein solution and the generator's current was set at 2.5 mA and delivered for 4 min. A custom RRS setup was used for detecting lutein in the inner sclera, choroid, retinal periphery and macula of treated samples and controls. Forty minutes after iontophoresis, the inner sclera, choroid and retinal periphery were greatly enriched with lutein (P < .05); no lutein was found in the same ocular regions of non-treated samples. In the same period, the average concentration of lutein in the macula (4.8 ± 1.7 ng/mm ) of treated samples was 1.3 times greater than controls (3.7 ± 1.0 ng/mm ; P = .4). Scleral iontophoresis was shown to be effective in delivering lutein to the human retina. Future studies will aim at assessing if this therapeutic strategy is valuable to enrich the macular pigment in human subjects.

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“…20 Importantly, preclinical studies showed that iontophoresis employing low-current densities is safe and does not induce pathological structural changes in the cornea. [21][22][23][24] Ocular iontophoresis has also been explored as a delivery mode for iodide to treat dry eye 25,26 and for 6-hydroxydopamine to treat glaucoma, 27 but these applications did not advance into clinical practice. 27 Iontophoresis has only more recently become accepted by the clinical community as a promising technique for facilitating ocular delivery.…”

Section: Iontophoresis Technologymentioning

confidence: 99%

“…29 Further, biweekly trans-scleral iontophoresis of dexamethasone phosphate solution at current doses of 10, 14, and 20 mA-min over 24 weeks appeared safe in rabbits, with no treatment-related effects on intraocular pressure (IOP), electroretinography, or any histopathology. 24 The therapeutic use of an iontophoresis device (EyeGate Pharmaceuticals, Inc., Waltham, MA) to deliver a corticosteroid was initially explored clinically in 17 patients who experienced active graft rejection after a penetrating keratoplasty. 23 Iontophoretic applications of 62.5 mg/mL methylprednisolone sodium succinate were delivered once a day over 3 consecutive days using an electric current of 1.5 mA for 4 min.…”

Section: Evolution Of Trans-scleral Corticosteroid Delivery Using Ionmentioning

confidence: 99%

Ophthalmic Drug Delivery Using Iontophoresis: Recent Clinical Applications

Pérez¹,

Wirostko

Korenfeld

et al. 2020

Journal of Ocular Pharmacology and Therapeutics

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Background: Iontophoresis is a noninvasive delivery system designed to overcome barriers to ocular penetration of topical ophthalmic medications by employing a low-amplitude electrical current to promote the migration of a charged drug substance across biological membranes. Trans-scleral iontophoresis of dexamethasone phosphate has demonstrated dramatically increased intraocular concentrations of dexamethasone in rabbit ocular tissues compared with topical instillation, including 50-to 100-fold greater aqueous humor concentrations. Methods: This article reviews available data on recent clinical applications of iontophoretic ophthalmic drug delivery. Results: The EyeGate II delivery system (EGDS) is a trans-scleral iontophoresis system that has been used in conjunction with EGP-437, a proprietary-charged formulation of dexamethasone phosphate for iontophoretic delivery. In patients with noninfectious anterior uveitis, EGP-437, delivered through 2 iontophoretic treatments using the EGDS, demonstrated similar efficacy to topical prednisolone acetate 1% eye drops instilled 8 times daily over 28 days, suggesting the potential to decrease or eliminate the need for daily dosing of topical steroids in this patient population. Other applications for EGP-437 delivered through the EGDS that have been explored in clinical trials include treatment of dry eye, postsurgical inflammation and pain, and scleritis. In addition, transcorneal iontophoresis has been used outside of the United States to enhance riboflavin penetration in patients undergoing corneal cross-linking as therapy for progressive keratoconus. Conclusions: The reviewed studies demonstrate the feasibility of using iontophoresis to enhance drug delivery to ocular tissues and support the potential of this noninvasive technique across a range of ophthalmic indications.

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Evaluation of Ocular and General Safety Following Repeated Dosing of Dexamethasone Phosphate Delivered by Transscleral Iontophoresis in Rabbits

Abstract: 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.

Cited by 25 publications

References 16 publications

A Novel Ocular Drug Delivery System of Dexamethasone Sodium Phosphate for Noninfectious Uveitis Treatment

A Novel Ocular Drug Delivery System of Dexamethasone Sodium Phosphate for Noninfectious Uveitis Treatment

Assessment of trans‐scleral iontophoresis delivery of lutein to the human retina

Ophthalmic Drug Delivery Using Iontophoresis: Recent Clinical Applications

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