Title : Monitorization of the neuroprotective formulation Brimonidine-Laponite over 6 months in a glaucoma murine
Abstract:
Brimonidine (Bri) is an ocularhypopressure drug widely used for glaucoma treatment as eye drops, and recent studies also showed to be protective to neuroretinal tissue. Intraocular administration needs of long-lasting delivery systems in order to decrease sight-threatened side effects and increase patient’s compliance. In this study, the nano-clay Laponite® (Lap) was used as a biocompatible carrier with the aim of obtaining intraocular sustained levels of Brimonidine. Bilateral glaucoma by Morrison’s model was induced in 60 Long Evans rats and Bri-Lap formulation was injected into the vitreous humor in right eyes at baseline, and 31 animals served as controls. To study clinical safety, ocular signs and intraocular pressure (with Tonolab®; TiolatOy Helsinki, Finland) were monitored weekly. Functional and structural studies were performed at 0-8-12- 18-24 weeks to analyze the neuroretinal tissue, by in vivo electroretinography (ERG)(Roland consult® RETIanimal ERG, Germany), high-resolution optical coherence tomography (OCT) (High Resolution-OCT Spectralis, Heidelberg® Engineering, Germany) and histological studies, respectively. For drug monitorization Bri-Lap quantification by high performance liquid chromatography mass spectrometry (HPLC-Mss), pharmacokinetic study and vitreous signal intensity by in vivo OCT were analyzed. Bri-Lap formulation was well tolerated, early decreased the intraocular pressure (17.36 ±4.10vs 25.26±3.69mmHg; p<0.001), exerted both structural -increased thickness of whole retina and axons of retinal ganglion cell (RGC) (25.60±1.67 vs 21.57±5.59; p=0.038) by OCT and cell count (23.00±0.39 vs 20.66±0.98; p=0.040) compared to non-treated eye- and functional -by maintaining higher amplitude ERG of RGC (41.20±8.75 vs 14.60±12.60; p=0.015)- neuroprotective effect up to 6 months. Ocular levels of Bri-Lap progressively decreased (intensity = 30 to 0.22) over follow-up being detectable up to 6 months. In conclusion, Laponite allowed intraocular sustained delivery of Brimonidine. A single eye injection of Bri-Lap formulation exerted both functional and structural protection of the neurorretinal tissue over 6 months
