Sustained Back Of The Eye Delivery Following Sub-tenon Administration Of Dexamethasone-loaded PLGA Microspheres In Rabbits

Abstract

Purpose: : Quantification and pharmacokinetics evaluation of dexamethasone in ocular tissues after sub-tenon administration of dexamethasone-loaded PLGA microspheres in rabbits. Dexamethasone is widely used in ophthalmology to treat several ocular diseases affecting the posterior segment. Due to short half-live of dexamethasone, repeated intraocular injections are employed in the treatment of most of these diseases. Controlled drug delivery systems, such as as microspheres (MPh) are being designed to avoid frequent injections. MPhs based on a biodegradable polymer (PLGA) have been developed to release dexamethasone in vitro for 65 days. MPhs can be periocularly administered as a conventional injection with less risk of adverse effects than intravitreal administration.

Methods: : Sterilized dexamethasone-loaded PLGA microspheres (5 mg of microspheres, dose: 828 µg of Dexamethasone) were administered by sub-tenon injection to rabbits. Dexamethasone concentrations in rabbit ocular tissues (choroid-RPE, retina and vitreous) were evaluated at different time points (1, 2, 4 and 6 weeks after injection). Samples were treated and the drug was quantified by means of electrospray ionization MS/MS analysis after separation by HPLC.

Results: : After administration in rabbits, dexamethasone reached measurable concentrations in choroid-RPE, retina and vitreous during the six-weeks study. The tmax was observed at 2 weeks post-administration in the three tissues evaluated, with Cmax values of 579.02 ng/g, 1,749.65 ng/g and 69.19 ng/mL for choroid-RPE, retina and vitreous respectively. Calculations of area under the concentration-time curve (AUC0,42d) in the target tissue (retina) were performed as measurement of drug bioavailability, with a value of 21,337.52 ng day/g.

Conclusions: : According to the results obtained in this work, the microsphere formulation developed is suitable for sustained transscleral delivery of dexamethasone. Periocular microspheres can be considered as a potential alternative to dexamethasone intravitreal administrations indicated for the treatment of diseases affecting the posterior segment of the eye.

Keywords: corticosteroids • retina