Engineering a novel water-in-oil biocompatible microemulsion system for the ocular delivery of dexamethasone sodium phosphate in the treatment of acute uveitis

Abstract

Due to their unique characteristics, microemulsions (ME) represent one of the most promising delivery systems which can conquer poor ocular drug bioavailability providing long residence time. Development of a ME system, relying on the use of a safe and non-irritant surfactant combination derived from sustainable resources and which can consolidate the small ME droplets, is the goal of this work. Herein, we report the design and characterization of a novel biocompatible, eco-friendly ME system loaded with the hydrophilic dexamethasone sodium phosphate (DEXP) using a novel surfactant mixture composed of D-α-tocopherol polyethylene glycol succinate (TPGS) and Plantacare® (coco-Glycosides). Capryol™ PGMC and double-distilled water were used as the respective oil and aqueous phases and the MEs were prepared by the water titration method, suitable for scaling up. Optimization of ME formulae was conducted by varying Plantacare® grades, TPGS to Plantacare® mass ratios and drug loading. The formulae were characterized in terms of physical appearance, droplet size (PS), size distribution (PDI), zeta potential (ZP), and stability. The optimized DEXP-loaded ME formula attained acceptable PS, PDI, and ZP values of 43 ± 5 nm, 0.35 ± 0.07, −12 ± 4 mV, respectively. TEM images confirmed a small PS ≤ 100 nm. The in vivo safety of ME was proved by the Draize test. The ME formula prompted excellent mucoadhesion and transcorneal permeation. The confocal studies showed deep penetration into the rabbits’ corneas. In vivo studies using endotoxin-induced uveitis showed high ocular efficacy and a significant reduction in inflammatory cells, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The obtained results elect the novel engineered ME system as a promising tool for the ocular delivery of hydrophilic moieties in the management of various ophthalmic diseases.