Dexamethasone delivery to the ocular posterior segment by sustained-release Laponite formulation.

Prieto, Esther; Cardiel, Maria Jose; Vispe, Eugenio; Idoipe, Miriam; Garcia-Martin, Elena; Fraile, Jose Maria; Polo, Vicente; Mayoral, Jose Antonio; Pablo, Luis Emilio; Rodrigo, Maria Jesus

This paper presents a novel nanoformulation for sustained-release delivery of dexamethasone to the ocular posterior segment using a Laponite carrier (DEX/LAP 1:10 w/w formulation; 10 mg/ml). In vivo ocular feasibility and pharmacokinetics after intravitreal and suprachoroidal administration in rabbit eyes are compared against intravitreal administration of a DEX solution (1 mg/ml). Thirty rabbit eyes were injected with the DEX/LAP formulation (15 suprachoroid / 15 intravitreous). Ophthalmological signs were monitored at day 1 and at weeks 1-4-12-24 post-administration. Three eyes per sample time point were used to quantify DEX concentration using high-performance liquid chromatography-mass spectrometry. The ocular tissues' pharmacokinetic parameters (lens, vitreous humour, choroid-retina unit and sclera) were studied. DEX/LAP was well tolerated under both administration methods. Peak intraocular DEX levels from the DEX/LAP were detected in the vitreous humour after both deliveries soon after administration. The vitreous area under the curve was significantly greater after both DEX/LAP deliveries (intravitreal: 205968.47; suprachoroidal: 11442.22 ng/g*day) than after intravitreal administration of the DEX solution (317.17 ng/g*day). Intravitreal DEX/LAP delivery extended higher vitreous DEX levels up to week 24 (466.32 ± 311.15 ng/g). With suprachoroidal delivery, DEX levels were detectable in the choroid-retina unit (12.04 ± 20.85 ng/g) and sclera (25.46 ± 44.09 ng/g) up to week 24. This study demonstrated the intraocular feasibility of both suprachoroidal and intravitreal administration of the DEX/LAP formulation. The Laponite increased the intraocular retention time of dexamethasone when compared with conventional solutions. DEX/LAP could be considered a biocompatible and useful sustained-release formulation for treating posterior-pole eye diseases.