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      Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic

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          Abstract

          The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care, particularly in community settings. Transmucosal routes include intranasal, buccal, sublingual and rectal. They are non-invasive routes for systemic drug delivery with the possibility of self-administration, or administration by family caregivers. In addition, their ability to offer rapid onset of action with reduced first-pass metabolism make them suitable for use in palliative and end-of-life care to provide fast relief of symptoms. This is particularly important in COVID-19, as patients can deteriorate rapidly. Despite the advantages, these routes of administration face challenges including a relatively small surface area for effective drug absorption, small volume of fluid for drug dissolution and the presence of a mucus barrier, thereby limiting the number of drugs that are suitable to be delivered through the transmucosal route. In this review, the merits, challenges and limitations of each of these transmucosal routes are discussed. The goals are to provide insights into using transmucosal drug delivery to bring about the best possible symptom management for patients at the end of life, and to inspire scientists to develop new delivery systems to provide effective symptom management for this group of patients.

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          Micro- and macrorheology of mucus.

          Mucus is a complex biological material that lubricates and protects the human lungs, gastrointestinal (GI) tract, vagina, eyes, and other moist mucosal surfaces. Mucus serves as a physical barrier against foreign particles, including toxins, pathogens, and environmental ultrafine particles, while allowing rapid passage of selected gases, ions, nutrients, and many proteins. Its selective barrier properties are precisely regulated at the biochemical level across vastly different length scales. At the macroscale, mucus behaves as a non-Newtonian gel, distinguished from classical solids and liquids by its response to shear rate and shear stress, while, at the nanoscale, it behaves as a low viscosity fluid. Advances in the rheological characterization of mucus from the macroscopic to nanoscopic levels have contributed critical understanding to mucus physiology, disease pathology, and the development of drug delivery systems designed for use at mucosal surfaces. This article reviews the biochemistry that governs mucus rheology, the macro- and microrheology of human and laboratory animal mucus, rheological techniques applied to mucus, and the importance of an improved understanding of the physical properties of mucus to advancing the field of drug and gene delivery.
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            Is Open Access

            Evaluation of intranasal delivery route of drug administration for brain targeting

            The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.
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              Mechanism of intranasal drug delivery directly to the brain

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                Author and article information

                Journal
                Adv Drug Deliv Rev
                Adv Drug Deliv Rev
                Advanced Drug Delivery Reviews
                Elsevier B.V.
                0169-409X
                1872-8294
                1 November 2020
                1 November 2020
                Affiliations
                [a ]Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region
                [b ]School of Pharmacy, University of Nottingham, University Park, Nottingham, United Kingdom
                [c ]Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Australia
                [d ]Helen and Douglas House, Oxford University Hospitals NHS Foundation Trust, United Kingdom
                [e ]Oxford University Hospitals NHS Foundation Trust, United Kingdom
                [f ]Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom
                [g ]Centre for Medicines Optimisation Research and Education (CMORE), Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom
                Author notes
                [* ]Corresponding author.
                Article
                S0169-409X(20)30165-4
                10.1016/j.addr.2020.10.018
                7603972
                33137363
                54285661-38c1-4f3b-944a-ff8b4b092cca
                © 2020 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 23 September 2020
                : 25 October 2020
                : 27 October 2020
                Categories
                Article

                benzodiazepine,buccal,end-of-life drug,intranasal,opioid,rectal,sublingual,systemic delivery

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