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      Pharmacokinetics of intravitreal antibiotics in endophthalmitis

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          Abstract

          Intravitreal antibiotics are the mainstay of treatment in the management of infectious endophthalmitis. Basic knowledge of the commonly used intravitreal antibiotics, which includes their pharmacokinetics, half-life, duration of action and clearance, is essential for elimination of intraocular infection without any iatrogenic adverse effect to the ocular tissue. Various drugs have been studied over the past century to achieve this goal. We performed a comprehensive review of the antibiotics which have been used for intravitreal route and the pharmacokinetic factors influencing the drug delivery and safety profile of these antibiotics. Using online resources like PubMed and Google Scholar, articles were reviewed. The articles were confined to the English language only. We present a broad overview of pharmacokinetic concepts fundamental for use of intravitreal antibiotics in endophthalmitis along with a tabulated compendium of the intravitreal antibiotics using available literature. Recent advances for increasing bioavailability of antibiotics to the posterior segment with the development of controlled drug delivery devices are also described.

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          Most cited references 68

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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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            Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles.

            To study the kinetics of polylactide (PLA) nanoparticle (NP) localization within the intraocular tissues and to evaluate their potential to release encapsulated material. A single intravitreous injection (5 micro L) of an NP suspension (2.2 mg/mL) encapsulating either Rh-6G (Rh) or Nile red (Nr) was performed. Animals were killed at various times, and the NPs localization within the intraocular tissues was studied by environmental scanning electron microscopy (ESEM), confocal microscopy, light microscopy histology, fluorescence microscopy, and immunohistochemistry. Eyes injected with blank NPs, free Rh, or PBS solution were used as the control. ESEM showed the flow of the NPs from the site of injection into the vitreous cavity and their rapid settling on the internal limiting membrane. Histology demonstrated the anatomic integrity of the injected eyes and showed no toxic effects. A mild inflammatory cell infiltrate was observed in the ciliary body 6 hours after the injection and in the posterior vitreous and retina at 18 to 24 hours. The intensity of inflammation decreased markedly by 48 hours. Confocal and fluorescence microscopy and immunohistochemistry showed that a transretinal movement of the NPs was gradually taking place with a later localization in the RPE cells. Rh encapsulated within the injected NPs diffused and stained the retina and RPE cells. PLA NPs were still present within the RPE cells 4 months after a single intravitreous injection. Intravitreous injection of PLA NPs appears to result in transretinal movement, with a preferential localization in the RPE cells. Encapsulated Rh diffuses from the NPs and stains the neuroretina and the RPE cells. The findings support the idea that specific targeting of these tissues is feasible. Furthermore, the presence of the NPs within the RPE cells 4 months after a single injection shows that a steady and continuous delivery of drugs can be achieved.
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              Cell culture models of the ocular barriers.

              The presence of tight barriers, which regulate the environment of ocular tissues in the anterior and posterior part of the eye, is essential for normal visual function. The development of strategies to overcome these barriers for the targeted ocular delivery of drugs, e.g. to the retina, remains a major challenge. During the last years numerous cell culture models of the ocular barriers (cornea, conjunctiva, blood-retinal barrier) have been established. They are considered to be promising tools for studying the drug transport into ocular tissues, and for numerous other purposes, such as the investigation of pathological ocular conditions, and the toxicological screening of compounds as alternative to in vivo toxicity tests. The further development of these in vitro models will require more detailed investigations of the barrier properties of both the cell culture models and the in vivo ocular barriers. It is the aim of this review to describe the current status in the development of cell culture models of the ocular barriers, and to discuss the applicability of these models in pharmaceutical research.
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                Author and article information

                Contributors
                Journal
                J Ophthalmic Inflamm Infect
                J Ophthalmic Inflamm Infect
                Journal of Ophthalmic Inflammation and Infection
                Springer
                1869-5760
                2014
                10 September 2014
                : 4
                : 22
                Affiliations
                [1 ]Retina and Uveitis Department, L V Prasad Eye Institute, GMR Varalaxmi Campus, 11-113/1, Hanumantha waka Junction, Visakhapatnam 530040, Andhra Pradesh, India
                [2 ]Srimati Kannuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, KAR Campus, Hyderabad 500034, Andhra Pradesh, India
                [3 ]Department of Ophthalmology, Bascom Palmer Eye Institute, Miami 33136, FL, USA
                Article
                s12348-014-0022-z
                10.1186/s12348-014-0022-z
                4306439
                Copyright © 2014 Mediknoda et al.; licensee Springer.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review

                Ophthalmology & Optometry

                intravitreal, antibiotics, pharmacokinetics, endophthalmitis

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