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      The PEG-PCL-PEG Hydrogel as an Implanted Ophthalmic Delivery System after Glaucoma Filtration Surgery; a Pilot Study

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          Abstract

          Currently, filtration surgery has been considered as the most effective therapy for glaucoma; however, the scar formation in the surgical area may often lead to failure to the procedure. An implanted drug delivery system may provide localized and sustained release of a drug over an extended period. Poly (ethylene glycol)-poly (ε-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel has been successfully synthesized and determined as thermosensitive and biocompatible. In order to overcome the limitations of common local ophthalmic medications, we investigated the function of a self-assembled PECE hydrogel as an intracameral injection-implanted drug carrier to inhibit the formation of postoperative scarring. Following bevacizumal-loaded hydrogel intracameral injection into rabbit eyes, the status of the bleb and filtration fistula formed following the filtering surgery were examined through pathologic evaluation. Due to the sustained release of bevacizumab from the hydrogel, neovascularization and scar formation were inhibited; moreover, there were no corneal abnormalities and other ocular tissue damage found in the rabbits. This suggests that the PECE hydrogel may be considered as the novel biomaterial with potential as a sustained release system in glaucoma filtering surgery. Further studies require in shedding the light on the subject.

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          Most cited references29

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          Novel injectable neutral solutions of chitosan form biodegradable gels in situ.

          A novel approach to provide, thermally sensitive neutral solutions based on chitosan/polyol salt combinations is described. These formulations possess a physiological pH and can be held liquid below room temperature for encapsulating living cells and therapeutic proteins; they form monolithic gels at body temperature. When injected in vivo the liquid formulations turn into gel implants in situ. This system was used successfully to deliver biologically active growth factors in vivo as well as an encapsulating matrix for living chondrocytes for tissue engineering applications. This study reports for the first time the use of polymer/polyol salt aqueous solutions as gelling systems, suggesting the discovery of a prototype for a new family of thermosetting gels highly compatible with biological compounds.
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            Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration.

            To report the short-term safety, biologic effect, and a possible mechanism of action of intravitreal bevacizumab in patients with neovascular age-related macular degeneration (AMD). Interventional, consecutive, retrospective case series. Eighty-one eyes of 79 patients with subfoveal neovascular AMD. Patients received intravitreal bevacizumab (1.25 mg) on a monthly basis until macular edema, subretinal fluid (SRF), and/or pigment epithelial detachment (PED) resolved. Ophthalmic evaluations included nonstandardized Snellen visual acuity (VA), complete ophthalmic examination, fluorescein angiography, and optical coherence tomography (OCT). Assessments of safety, changes in Snellen VA, OCT retinal thickness, and angiographic lesion characteristics were performed. No significant ocular or systemic side effects were observed. Most patients (55%) had a reduction of >10% of baseline retinal thickness at 1 week after the injection. At 4 weeks after injection, 30 of 81 eyes demonstrated complete resolution of retinal edema, SRF, and PEDs. Of the 51 eyes with 8 weeks' follow-up, 25 had complete resolution of retinal thickening, SRF, and PEDs. At 1, 4, 8,and 12 weeks, the mean retinal thickness of the central 1 mm was decreased by 61, 92, 89, and 67 mum, respectively (P<0.0001 for 1, 4, and 8 weeks and P<0.01 for 12 weeks). At 4 and 8 weeks, mean VA improved from 20/200 to 20/125 (P<0.0001). Median vision improved from 20/200 to 20/80(-) at 4 weeks and from 20/200 to 20/80 at 8 weeks. Short-term results suggest that intravitreal bevacizumab (1.25 mg) is well tolerated and associated with improvement in VA, decreased retinal thickness by OCT, and reduction in angiographic leakage in most patients, the majority of whom had previous treatment with photodynamic therapy and/or pegaptanib. Further evaluation of intravitreal bevacizumab for the treatment of choroidal neovascularization is warranted.
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              A reversibly antigen-responsive hydrogel.

              Stimuli-responsive hydrogels that undergo abrupt changes in volume in response to external stimuli such as pH, temperature and solvent composition have potential applications in biomedicine and the creation of 'intelligent' materials systems, for example as media for drug delivery, separation processes and protein immobilization. Hydrogels have been reported that respond to pH, temperature, electric fields and saccharides. For some biomedical applications it would be very useful to have a material whose swelling response was dictated by a specific protein. Here we report such a material, which swells reversibly in a buffer solution in response to a specific antigen. The hydrogel was prepared by grafting the antigen and corresponding antibody to the polymer network, so that binding between the two introduces crosslinks in the network. Competitive binding of the free antigen triggers a change in gel volume owing to breaking of these non-covalent crosslinks. In addition, we show that the hydrogel displays shape-memory behaviour, and that stepwise changes in antigen concentration can induce pulsatile permeation of a protein through the network.
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                Author and article information

                Journal
                Med Hypothesis Discov Innov Ophthalmol
                mehdiophth
                Medical Hypothesis, Discovery and Innovation in Ophthalmology
                Medical Hypothesis, Discovery & Innovation Ophthalmology
                2322-4436
                2322-3219
                Spring 2014
                : 3
                : 1
                : 3-8
                Affiliations
                [1 ]Department of Ophthalmology,
                [2 ] Department of Otorhinolaryngology,
                [3 ]Department of Pathology, the Affiliated Hospital of Luzhou Medical College, Luzhou of Sichuan Province, 646000, China,
                [4 ]State Key Laboratory of Biotherapy and Cancer Center ,  West China Hospital , Sichuan  University,  Chengdu ,  Sichuan  Province 610041,  China
                Author notes
                Correspondence to: Dr Ling Yu, Department of ophthalmology, the Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, 646000 China, Tel: +86 830 3165631; Fax: +86 830 2392753, E-mail: oculistlingyu@hotmail.com
                Article
                mehdiophth-3-003
                4010917
                24804274
                5abb8b95-1d25-4abc-9576-99c3f00662cd
                © 2014, Medical Hypothesis, Discovery & Innovation (MEHDI) Ophthalmology Journal

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Original Article

                peg-pcl-peg,pece hydrogel,ophthalmic delivery system,glaucoma filtration surgery,filtration fistula

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