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      Nanotechnology-based strategies for treatment of ocular disease.

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          Abstract

          Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops, injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new, highly effective and important ocular nanomedicines.

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          Most cited references92

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          Preservatives in eyedrops: the good, the bad and the ugly.

          There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e., allergic, toxic, or inflammatory, as well as the respective roles of the active compound and the preservative in inducing the toxic and/or proinflammatory effects of ophthalmic solutions, is still being debated. The most frequently used preservative, benzalkonium chloride (BAK), has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies. As a quaternary ammonium, this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The mechanisms causing these effects have not been fully elucidated, although the involvement of immunoinflammatory reactions with the release of proinflammatory cytokines, apoptosis, oxidative stress, as well as direct interactions with the lipid components of the tear film and cell membranes have been well established. Preservative-induced adverse effects are therefore far from being restricted to only allergic reactions, and side effects are often very difficult to identify because they mostly occur in a delayed or poorly specific manner. Care should therefore be taken to avoid the long-term use of preservatives, otherwise a less toxic alternative to BAK should be developed, as this weakly allergenic but highly toxic compound exerts dose- and time-dependent effects. On the basis of all these experimental and clinical reports, it would be advisable to use benzalkonium-free solutions whenever possible, especially in patients with the greatest exposure to high doses or prolonged treatments, in those suffering from preexisting or concomitant ocular surface diseases, and those experiencing side effects related to the ocular surface. Indeed, mild symptoms should not be underestimated, neglected, or denied, because they may very well be the apparent manifestations of more severe, potentially threatening subclinical reactions that may later cause major concerns. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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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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              The physics, biophysics and technology of photodynamic therapy.

              Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components -- light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.
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                Author and article information

                Journal
                Acta Pharm Sin B
                Acta pharmaceutica Sinica. B
                Elsevier BV
                2211-3835
                2211-3835
                May 2017
                : 7
                : 3
                Affiliations
                [1 ] College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
                [2 ] Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience; and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
                [3 ] University of Chinese Academy of Sciences. Beijing 100049, China.
                Article
                S2211-3835(16)30085-5
                10.1016/j.apsb.2016.09.001
                5430571
                28540165
                97757f15-6c20-404f-b50c-6e13686c4ec7
                History

                Therapy,Ocular drug delivery,Ocular disease,Nanosystems,Nanocarrier,Eye,Diagnosis

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