الفهرس 
Chapter 1 : Introduction
Anatomy of the EyeOnly 14 pages are availabe for public view
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Abstract
Persistent or repeated elevation of intraocular pressure (IOP) is a primary risk factor of visual field loss in glaucoma, therefore IOP reduction is the first-line therapeutic option in the disease management. Unfortunately, the current therapies are associated with a lot of deficiencies including several daily dosing, reduced efficacy and systemic side effects all of which resulted in poor patient compliance. Previously we have identified Calcium voltage-gated channel auxiliary subunit Alpha2delta 1 gene (Cacna2d1) as a novel modulator of IOP and confirmed that pregabalin targeted CACNA2D1 in eye tissues (ciliary body and trabecular meshwork) to lower IOP in a dose-dependent manner. The research presented in this dissertation aimed to develop a once-daily ocular pregabalin-loaded multiple water-in-oil-in-water microemulsion eye drops. Several in vitro and in vivo evaluations were used to characterize the prepared ophthalmic formulations. Also stability study at 5°C, 25°C, 30°C and 40°C was conducted for four months. All the formulations components were carefully selected to be highly biocompatible that provided a highly transparent eye drops with a miniscule droplet size (<20nm) accompanied with a good shelf life stability. The special engineering of the microemulsion eye drops succeeded to provide a continuous
pregabalin release for up to 24h. Slit-lamp biomicroscopic exams and the cell toxicity study demonstrated that the developed ocular formulations were non-toxic. The in vivo study using Dutch belted rabbits showed that the microemulsion formulation markedly enhanced the efficacy and prolonged the duration of pregabalin IOP-lowering effect. Interestingly, a single DROP of pregabalin microemulsion induced 42.3±2.6% IOP reduction that returned to baseline at 32.7±1.3h from application (AUC=169.9±13.4 mmHg.h). In the absence of the microemulsion system, the same drug produced only 29.4±1.4% IOP reduction that returned to baseline at 9.3±0.7h (AUC=39±4 mmHg.h). Finally, the developed multiple microemulsion is a promising carrier that sustained the release and prolonged the duration of action of pregabalin and could be a carrier for any other water-soluble drug.