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Sanjib Kiumar Das, Stuart Williams, Janet Tully, Rozemarijn S Verhoeven, Mari Yang, Tomas Navratil, Rhett Schiffman; Precision Size and Shape Extended Release Intravitreal Dexamethasone Implants. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3278. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Intraocular implants for the delivery of steroids are used for treatment of retinal vein occlusion (RVO), diabetic macular edema (DME) and uveitis. Approved therapies include the biodegradable Ozurdex (dexamethasone) and the non-biodegradable Iluvien (fluocinolone acetonide). Ozurdex is approved for injection every 6 months, though efficacy commonly lasts no more than 2-3 months; Iluvien efficacy lasts for approximately 30 months. A biodegradable dexamethasone implant with duration of action of approximately 6 months would be clinically desirable. Herein, we characterize the in vitro and in vivo release profile of a biodegradable intraocular implant that can deliver therapeutically effective amounts of dexamethasone into the vitreous.
Dexamethasone-polymer implants were fabricated using the proprietary PRINT® technology. Implant size, shape and morphology were determined by Scanning Electron Microscopy (SEM). Dexamethasone content and release were measured by RP-HPLC. In vivo tolerability and pharmacokinetics were evaluated in albino rabbits. Rabbits received intravitreal injection of PRINT implants and levels of dexamethasone in vitreous humor, aqueous humor, and retina were determined at day 28, 56, and 84 by HPLC. Tolerability was assessed by ocular exams including slit lamp biomicroscopy and indirect ophthalmoscopy.
Extended release dexamethasone implants were fabricated with a high degree of mass uniformity and dexamethasone content. Implants were able to release dexamethasone in a near zero-order manner for 6 months in vitro. Unlike Ozurdex, tissue exposure present remained consistent with minimal burst and greatly exceeded therapeutic levels in the retina and vitreous over the entire in vivo evaluation over 3 month period. Dexamethasone concentration in the tissues remained consistent throughout the study, indicating no burst release of drug for the duration of the study. The drug exposure was highest in the retina, and substantially less exposure was observed in aqueous humor.
Extended release dexamethasone implants were fabricated with uniform size, shape and dose. These formulations demonstrate sustained release of steroid for 6 months in vitro. In a 3 month rabbit PK study, implants dosed were able to consistently maintain therapeutically relevant amounts of dexamethasone in the retina and vitreous for the full duration of the study and were well tolerated.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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