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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Synthesis, Characterization, and Toxicity Assessment of Pluronic F127-Functionalized Graphene Oxide on the Embryonic Development of Zebrafish ( Danio rerio)

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          Abstract

          Background

          In the current literature, there are ongoing debates on the toxicity of graphene oxide (GO) that demonstrate contradictory findings regarding its toxicity profile. As a potential drug carrier, these findings are very concerning due to the safety concerns in humans, as well as the dramatic rise of GO being excreted into the environment. Therefore, there is an imperative need to mitigate the potential toxicity of GO to allow for a safer application in the future.

          Purpose

          The present study aims to address this issue by functionalizing GO with Pluronic F127 (PF) as a means to mitigate toxicity and resolve the biocompatibility of GO. Although results from previous studies generally indicated that Pluronic functionalized GO exhibits relatively low toxicity to living organisms, reports that emphasize on its toxicity, particularly during embryonic developmental stage, are still scarce.

          Methods

          In the present study, two different sizes of native GO samples, GO and NanoGO, as well as PF-functionalized GO, GO-PF and NanoGO-PF, were prepared and characterized using DLS, UV-Vis, Raman spectroscopy, FTIR, and FESEM analyses. Toxicological assessment of all GO samples (0–100 µg/mL) on zebrafish embryonic developmental stages (survival, hatching and heart rates, and morphological changes) was recorded daily for up to 96 hours post-fertilization (hpf).

          Results

          The toxicity effects of each GO sample were observed to be higher at increasing concentrations and upon prolonged exposure. NanoGO demonstrated lower toxicity effects compared to GO. GO-PF and NanoGO-PF were also found to have lower toxicity effects compared to native GO samples. GO-PF showed the lowest toxicity response on zebrafish embryo.

          Conclusion

          These findings highlight that toxicity is dependent on the concentration, size, and exposure period of GO. Functionalization of GO with PF through surface coating could potentially mitigate the toxicity effects of GO in embryonic developmental stages, but further investigation is warranted for broader future applications.

          Most cited references69

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          Improved synthesis of graphene oxide.

          An improved method for the preparation of graphene oxide (GO) is described. Currently, Hummers' method (KMnO(4), NaNO(3), H(2)SO(4)) is the most common method used for preparing graphene oxide. We have found that excluding the NaNO(3), increasing the amount of KMnO(4), and performing the reaction in a 9:1 mixture of H(2)SO(4)/H(3)PO(4) improves the efficiency of the oxidation process. This improved method provides a greater amount of hydrophilic oxidized graphene material as compared to Hummers' method or Hummers' method with additional KMnO(4). Moreover, even though the GO produced by our method is more oxidized than that prepared by Hummers' method, when both are reduced in the same chamber with hydrazine, chemically converted graphene (CCG) produced from this new method is equivalent in its electrical conductivity. In contrast to Hummers' method, the new method does not generate toxic gas and the temperature is easily controlled. This improved synthesis of GO may be important for large-scale production of GO as well as the construction of devices composed of the subsequent CCG.
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            Stages of embryonic development of the zebrafish.

            We describe a series of stages for development of the embryo of the zebrafish, Danio (Brachydanio) rerio. We define seven broad periods of embryogenesis--the zygote, cleavage, blastula, gastrula, segmentation, pharyngula, and hatching periods. These divisions highlight the changing spectrum of major developmental processes that occur during the first 3 days after fertilization, and we review some of what is known about morphogenesis and other significant events that occur during each of the periods. Stages subdivide the periods. Stages are named, not numbered as in most other series, providing for flexibility and continued evolution of the staging series as we learn more about development in this species. The stages, and their names, are based on morphological features, generally readily identified by examination of the live embryo with the dissecting stereomicroscope. The descriptions also fully utilize the optical transparancy of the live embryo, which provides for visibility of even very deep structures when the embryo is examined with the compound microscope and Nomarski interference contrast illumination. Photomicrographs and composite camera lucida line drawings characterize the stages pictorially. Other figures chart the development of distinctive characters used as staging aid signposts.
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              Graphene-based nanomaterials for drug delivery and tissue engineering.

              Nanomaterials offer interesting physicochemical and biological properties for biomedical applications due to their small size, large surface area and ability to interface/interact with the cells/tissues. Graphene-based nanomaterials are fast emerging as "two-dimensional wonder materials" due to their unique structure and excellent mechanical, optical and electrical properties and have been exploited in electronics and other fields. Emerging trends show that their exceptional properties can be exploited for biomedical applications, especially in drug delivery and tissue engineering. This article presents a comprehensive review of various types and properties of graphene family nanomaterials. We further highlight how these properties are being exploited for drug delivery and tissue engineering applications.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                ijn
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                28 October 2020
                2020
                : 15
                : 8311-8329
                Affiliations
                [1 ]Laboratory of Animal Biochemistry and Biotechnology, Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia , Serdang, Selangor 43400, Malaysia
                [2 ]Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia , Serdang, Selangor 43400, Malaysia
                [3 ]Department of Chemical and Environmental Engineering, Faculty of Engineering, Universiti Putra Malaysia , Serdang, Selangor 43400, Malaysia
                [4 ]Institute of Advanced Technology, Faculty of Engineering, Universiti Putra Malaysia , Serdang, Selangor 43400, Malaysia
                Author notes
                Correspondence: Suhaili ShamsiLaboratory of Animal Biochemistry and Biotechnology, Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia , Serdang, Selangor43400, MalaysiaTel +603-9769 7964Fax +603-9769 7590 Email sh_suhaili@upm.edu.my
                Author information
                http://orcid.org/0000-0002-9308-6274
                http://orcid.org/0000-0002-5450-4496
                Article
                271159
                10.2147/IJN.S271159
                7604977
                be17356a-a124-40c0-bf72-344a830e0e7f
                © 2020 Shamsi et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 13 July 2020
                : 29 August 2020
                Page count
                Figures: 11, Tables: 2, References: 70, Pages: 19
                Funding
                Funded by: Ministry of Higher Education of Malaysia;
                This research was funded by research grants from Ministry of Higher Education of Malaysia, namely Fundamental Research Grant Scheme (FRGS), grant number 04-01-18-1931FR and Universiti Putra Malaysia (GP/IPM/2016/9513200). Authors acknowledge the facilities, scientific and technical assistance from the Institute of Advanced Technology (ITMA) and Institute of Biosciences (IBS) at Universiti Putra Malaysia.
                Categories
                Original Research

                Molecular medicine
                graphene oxide,pluronic,nanomaterial,toxicity,embryogenesis
                Molecular medicine
                graphene oxide, pluronic, nanomaterial, toxicity, embryogenesis

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