The dexamethasone drug delivery system: Indications and evidence

Abstract

The dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.

Biocompatibility of Poly(ester amide) (PEA) Microfibrils in Ocular Tissues

“…Biodegradable materials such as Ozurdex ® , which can be injected into the vitreous humor, release the drug irregularly. Additionally, the degradation products cause transient acidification of the vitreous humor and are not compatible with many drug species, such as biological therapeutics [1,12,15].…”

“…Currently, micro-and nanoparticles prepared from linear, biodegradable polyesters such as poly(lactic-co-glycolic acid) (PLGA) are used [11] and in 2009 an injectable PLGA intravitreal insert, OZURDEX ® , was approved by the FDA and is used successfully for the treatment of macular edema by releasing dexamethasone over a period of about three months [2,12]. PLGA is not used widely for intraocular drug delivery, in part because the kinetics of degradation and drug release are irregular.…”

“…There is an initial burst of drug release, followed by a phase of sustained release and a final phase in which all remaining drug is set free [1,13]. In addition to the asymmetrical release of drug, PLGA is hydrolyzed into lactic acid and glycolic acid, which transiently decrease vitreous humor to pH 7 and increases the risk of inflammation before being metabolized [12,14]. In addition, PLGA has been reported to show low compatibility with acid sensitive bio-pharmaceuticals [14,15].…”

Reservoir-Based Polymer Drug Delivery Systems

“…4,5,32 Currently, there are only three implants for the eye that have been approved by the FDA: Retisert, Vitrasert, 33 and Ozurdex. 34 Retisert, marketed by Bausch & Lomb, is an intraocular implant that contains fluocinolone acetonide (FA), to treat noninfectious uveitis. Retisert is composed of an FA tablet containing microcrystalline cellulose, magnesium stearate, and PVA.…”

Signal Transduction Pathways in use of Dexamethasone Implant in the Eye

“…Glucocorticoids have an important role in the treatment of intraocular diseases with an inflammatory origin. Thanks to their potent anti-inflammatory effects, their ability to decrease vascular permeability, inhibiting fibrin deposits and leukocyte motility, suppressing the migration of inflammatory cells, stabilizing endothelial tight junctions, inhibiting the synthesis of Vascular Endothelial Growth Factor (VEGF), Prostaglandins (PGs) and other cytokines and steroid-responsive gene transcription [3]. Intravitreal usage of a 0.7 mg dexamethasone implant (Ozurdex ® Allergan, Ireland), which is a corticosteroid with proven efficacy, obtained FDA approval in 2009 for the treatment of retinal vein occlusion, diabetic macular edema and non-infectious uveitis [4].…”