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Browsing by Subject "pintavaraus"

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  • Turunen, Tiina (2016)
    Posterior eye segment diseases, such as age-related macular degeneration, are leading causes of preventable visual impairment in the developed countries. Direct intravitreal injections are currently routinely used to deliver therapeutic agents most efficiently to posterior eye segment. Regular injections can however cause ocular complications and some drugs may also be toxic to ocular tissues at high local concentrations of free drug. Different nano-sized particulate systems have been extensively studied as possible drug delivery systems for intravitreal administration offering sustained, local drug action with controlled release. The vitreous gel can form a barrier for diffusion of particles due to its macromolecular structure and composition. Furthermore, ageing and different disease states cause changes in the vitreous structure possibly resulting in shift in the intravitreal movement of particulate systems. In the literature part of this Master's thesis ocular drug delivery is reviewed with main focus on drug targeting in the posterior eye segment. In the experimental work liposomes with different lipid compositions and surface charges were prepared as model particulate systems to evaluate the intravitreal diffusion of nanoparticles with confocal microscope. Furthermore, the influence of aging on the intravitreal diffusion was modeled by enzymatic degradation of the vitreous gel structure. It is discovered that vitreous gel hinders the movement of nanoparticles. Level of hindrance depends on particle's characteristics. 100-200 nm anionic particles move quite freely in the negatively charged vitreous gel. Similarly sized cationic particles are immobile in the vitreous due to electrostatic interactions between surface of the cationic particle and anionic glycosaminoglycans in the vitreous. 1 µm anionic and cationic particles are sterically trapped inside the vitreous meshwork created by the 3-dimensional biopolymer network of the vitreal macromolecules. Vitreous liquefaction increases the diffusion rate of nanoparticles but the clinical impact on ocular pharmacokinetics needs further research.