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      Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules

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          Abstract

          A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields.

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          Most cited references293

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          Designing hydrogels for controlled drug delivery

          Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
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            Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
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              Hydrogels in pharmaceutical formulations.

              N. Peppas (2000)
              The availability of large molecular weight protein- and peptide-based drugs due to the recent advances in the field of molecular biology has given us new ways to treat a number of diseases. Synthetic hydrogels offer a possibly effective and convenient way to administer these compounds. Hydrogels are hydrophilic, three-dimensional networks, which are able to imbibe large amounts of water or biological fluids, and thus resemble, to a large extent, a biological tissue. They are insoluble due to the presence of chemical (tie-points, junctions) and/or physical crosslinks such as entanglements and crystallites. These materials can be synthesized to respond to a number of physiological stimuli present in the body, such as pH, ionic strength and temperature. The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.
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                Author and article information

                Journal
                ACS Biomater Sci Eng
                ACS Biomater Sci Eng
                ab
                abseba
                ACS Biomaterials Science & Engineering
                American Chemical Society
                2373-9878
                17 June 2021
                13 September 2021
                : 7
                : 9 , Advanced Biomedical Hydrogels
                : 4102-4127
                Affiliations
                []Department of Chemistry, CICECO−Aveiro Institute of Materials, University of Aveiro 3810-193 Aveiro, Portugal
                []Cell Therapy and Regenerative Medicine Unit, Centro de Investigacións Científicas Avanzadas (CICA), Universidade da Coruña , 15071 A Coruña, Spain
                [§ ]Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology , 08028 Barcelona, Spain
                []CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN , 28029 Madrid, Spain
                []Wellcome-Wolfson Institute For Experimental Medicine, Queen’s University Belfast , 97 Lisburn Road, Belfast BT9 7BL, United Kingdom
                Author notes
                Author information
                https://orcid.org/0000-0002-4063-5735
                https://orcid.org/0000-0003-1682-498X
                https://orcid.org/0000-0002-2342-3765
                Article
                10.1021/acsbiomaterials.0c01784
                8919265
                34137581
                25feb755-dbaf-42e7-b322-f2e02f4d3f2e
                © 2021 American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 24 December 2020
                : 02 June 2021
                Funding
                Funded by: H2020 Marie SkÃ…?odowska-Curie Actions, doi 10.13039/100010665;
                Award ID: 712754
                Funded by: Xunta de Galicia, doi 10.13039/501100010801;
                Award ID: ED481B 2018/009
                Funded by: Ministerio de Ciencia e Innovación, doi 10.13039/501100004837;
                Award ID: RTI2018-099389-A-100
                Funded by: Ministerio de Economía y Competitividad, doi 10.13039/501100003329;
                Award ID: SEV-2014-0425
                Funded by: Ministerio de Economía y Competitividad, doi 10.13039/501100003329;
                Award ID: RYC2018-025617-I
                Funded by: Fundação para a Ciência e a Tecnologia, doi 10.13039/501100001871;
                Award ID: UIDP/50011/2020
                Funded by: Fundação para a Ciência e a Tecnologia, doi 10.13039/501100001871;
                Award ID: UIDB/50011/2020
                Funded by: Fundação para a Ciência e a Tecnologia, doi 10.13039/501100001871;
                Award ID: PTDC/BTM-MAT/31498/2017
                Categories
                Review
                Custom metadata
                ab0c01784
                ab0c01784

                biotherapeutics,hydrogels,controlled delivery,polysaccharides,tissue engineering,stimuli-responsiveness

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