In Vitro/In Vivo Evaluation of Dendrimeric Systems Forretinal Drug Delivery
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Ocular drug delivery is still a challenge due to its complex structure with many anatomical and physiological barriers. Delivering drugs to the back of the eye is especially harder because of barriers like cornea, sclera, blood-retina barrier; acellular vitreous structure, tear turnover. Thus retinal drug delivery can be only achieved by intravitreal route, which is an invasive technique that might cause serious ocular damage with repeated applications. However, posterior segment of the eye has many serious diseases, which increase the risk of blindness unless treated, such as age related macular degeneration, choroidal neovascularization and diabetic retinopathy. Dexamethasone (DEX) is a corticosteroid has been used for most of the ocular diseases including DR and macular edema. It is desirable to have a drug delivery system that can deliver DEX in a non-invasive manner, and yet achieve sufficiently high concentration in retina, or prolong the residence time and reduce the application frequency. Dendrimers are nanostructured polymers with high capability of interacting especially with hydrophobic drugs and improve their solubility and tissue permeation. In this study, various types of PAMAM dendrimers were used to prepare DEX complex or conjugate formulations in order to investigate the effect of dendrimers with different generations and charges, on DEX delivery to the retina, in terms of corneal and scleral permeability or the duration of the stay. DEX-PAMAM complex formulations are expected to show immediate release and a possible delivery system for topical or subconjunctival application. On the other hand DEXPAMAM conjugates were designed to obtain an extended release following subconjunctival or intravitreal injection. Thus, these formulations have been evaluated in different terms, based on their purpose of development.