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      Ocular Drug Delivery; Impact of in vitro Cell Culture Models

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          Abstract

          Normal vision depends on the optimal function of ocular barriers and intact membranes that selectively regulate the environment of ocular tissues. Novel pharmacotherapeutic modalities have aimed to overcome such biological barriers which impede efficient ocular drug delivery. To determine the impact of ocular barriers on research related to ophthalmic drug delivery and targeting, herein we provide a review of the literature on isolated primary or immortalized cell culture models which can be used for evaluation of ocular barriers. In vitro cell cultures are valuable tools which serve investigations on ocular barriers such as corneal and conjunctival epithelium, retinal pigment epithelium and retinal capillary endothelium, and can provide platforms for further investigations. Ocular barrier-based cell culture systems can be simply set up and used for drug delivery and targeting purposes as well as for pathological and toxicological research.

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          Most cited references98

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          Challenges and obstacles of ocular pharmacokinetics and drug delivery.

          Arto Urtti (2006)
          Modern biological research has produced increasing number of promising therapeutic possibilities for medical treatment. These include for example growth factors, monoclonal antibodies, gene knockdown methods, gene therapy, surgical transplantations and tissue engineering. Ocular application of these possibilities involves drug delivery in many forms. Ocular drug delivery is hampered by the barriers protecting the eye. This review presents an overview of the essential factors in ocular pharmacokinetics and selected pharmacological future challenges in ophthalmology.
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            Astrocytes induce blood-brain barrier properties in endothelial cells.

            The highly impermeable tight junctions between endothelial cells forming the capillaries and venules in the central nervous system (CNS) of higher vertebrates are thought to be responsible for the blood-brain barrier that impedes the passive diffusion of solutes from the blood into the extracellular space of the CNS. The ability of CNS endothelial cells to form a blood-brain barrier is not intrinsic to these cells but instead is induced by the CNS environment: Stewart and Wiley demonstrated that when avascular tissue from 3-day-old quail brain is transplanted into the coelomic cavity of chick embryos, the chick endothelial cells that vascularize the quail brain grafts form a competent blood-brain barrier; on the other hand, when avascular embryonic quail coelomic grafts are transplanted into embryonic chick brain, the chick endothelial cells that invade the mesenchymal tissue grafts form leaky capillaries and venules. It is, however, not known which cells in the CNS are responsible for inducing endothelial cells to form the tight junctions characteristic of the blood-brain barrier. Astrocytes are the most likely candidates since their processes form endfeet that collectively surround CNS microvessels. In this report we provide direct evidence that astrocytes are capable of inducing blood-brain barrier properties in non-neural endothelial cells in vivo.
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              Ocular novel drug delivery: impacts of membranes and barriers.

              Ocular drug delivery is an extremely challenging area due to its restrictive barrier functionalities. Drug transport via corneal/non-corneal routes involves several intricate biological processes such as drug penetration across the ocular barriers and transfer to the anterior or posterior chambers, thus the influence of these processes on the pharmacotherapy of the eye should be fully addressed. To pursue the impacts of such impediments in novel drug therapy, recent publications were reviewed regarding advanced strategies such as nanomedicines. The ocular barriers are highly specialized and selectively control the inward/outward traverse of compounds, hence a better understanding of these biological obstacles would provide a platform to advance ophthalmic drug therapy towards specified delivery/targeting with minimal adverse consequences.
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                Author and article information

                Journal
                J Ophthalmic Vis Res
                J Ophthalmic Vis Res
                JOVR
                Journal of Ophthalmic & Vision Research
                Ophthalmic Research Center
                2008-2010
                2008-322X
                October 2009
                : 4
                : 4
                : 238-252
                Affiliations
                [1 ]Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
                [2 ]School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
                Penn State Retina Research Group
                Author notes
                Correspondence to: Yadollah Omidi, PhD. Associate Professor of Pharmaceutical Nanobiotechnology; Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Tel: +98 411 3367914, Fax:+98 411 3367929; e-mail: yomidi@ 123456tbzmed.ac.ir
                Article
                JOVR-04-238
                3498862
                23198080
                5698db09-39aa-49b7-bc3d-7207eb16d4cc
                Copyright @ 2009
                History
                : 25 June 2009
                : 03 September 2009
                Categories
                Review Article

                Ophthalmology & Optometry
                drug delivery systems,in vitro
                Ophthalmology & Optometry
                drug delivery systems, in vitro

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