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      Resveratrol-Loaded Hydrogel Contact Lenses with Antioxidant and Antibiofilm Performance

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          Abstract

          Contact lenses (CLs) are prone to biofilm formation, which may cause severe ocular infections. Since the use of antibiotics is associated with resistance concerns, here, two alternative strategies were evaluated to endow CLs with antibiofilm features: copolymerization with the antifouling monomer 2-methacryloyloxyethyl phosphorylcholine (MPC) and loading of the antioxidant resveratrol with known antibacterial activity. MPC has, so far, been used to increase water retention on the CL surface (Proclear ® 1 day CLs). Both poly(hydroxyethyl methacrylate) (HEMA) and silicone hydrogels were prepared with MPC covering a wide range of concentrations (from 0 to 101 mM). All hydrogels showed physical properties adequate for CLs and successfully passed the hen’s egg-chorioallantoic membrane (HET-CAM) test. Silicone hydrogels had stronger affinity for resveratrol, with higher loading and a slower release rate. Ex vivo cornea and sclera permeability tests revealed that resveratrol released from the hydrogels readily accumulated in both tissues but did not cross through. The antibiofilm tests against Pseudomonas aeruginosa and Staphylococcus aureus evidenced that, in general, resveratrol decreased biofilm formation, which correlated with its concentration-dependent antibacterial capability. Preferential adsorption of lysozyme, compared to albumin, might also contribute to the antimicrobial activity. In addition, importantly, the loading of resveratrol in the hydrogels preserved the antioxidant activity, even against photodegradation. Overall, the designed hydrogels can host therapeutically relevant amounts of resveratrol to be sustainedly released on the eye, providing antibiofilm and antioxidant performance.

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          Mechanisms of biofilm resistance to antimicrobial agents

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            Cell sensitivity assays: the MTT assay.

            The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay is based on the conversion of MTT into formazan crystals by living cells, which determines mitochondrial activity. Since for most cell populations the total mitochondrial activity is related to the number of viable cells, this assay is broadly used to measure the in vitro cytotoxic effects of drugs on cell lines or primary patient cells. In this chapter the protocol of the assay is described including important considerations relevant for each step of the assay as well as its limitations and possible applications.
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              Antioxidant properties of resveratrol: A structure–activity insight

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                11 April 2021
                April 2021
                : 13
                : 4
                : 532
                Affiliations
                [1 ]Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; mariavivero.lopez@ 123456usc.es
                [2 ]Departamento de Microbiología, Facultad de Biología, Edificio CIBUS, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; andrea.muras@ 123456usc.es (A.M.); anamaria.otero@ 123456usc.es (A.O.)
                [3 ]Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; dianacristinasilva@ 123456tecnico.ulisboa.pt (D.S.); anapaula.serro@ 123456tecnico.ulisboa.pt (A.P.S.)
                [4 ]CIIEM, Instituto Superior de Ciências da Saúde Egas Moniz, Campus Universitário, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal
                Author notes
                [* ]Correspondence: angel.concheiro@ 123456usc.es (A.C.); carmen.alvarez.lorenzo@ 123456usc.es (C.A.-L.); Tel.: +34-881-815-239 (A.C.)
                Author information
                https://orcid.org/0000-0003-1603-9762
                https://orcid.org/0000-0002-6179-9296
                https://orcid.org/0000-0002-3315-5709
                https://orcid.org/0000-0003-0507-049X
                https://orcid.org/0000-0002-8546-7085
                Article
                pharmaceutics-13-00532
                10.3390/pharmaceutics13040532
                8069945
                33920327
                cd3576a2-78d8-4ce6-94e0-d9757352c3a9
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 15 February 2021
                : 06 April 2021
                Categories
                Article

                antibiofilm,antioxidant,drug-eluting contact lenses,microbial keratitis,endophthalmitis,device-related ocular infections

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