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      Current State and Future Directions of Intranasal Delivery Route for Central Nervous System Disorders: A Scientometric and Visualization Analysis

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          Abstract

          Background: The management of various central nervous system (CNS) disorders has been challenging, due to highly compact blood-brain barrier (BBB) impedes the access of most pharmacological agents to the brain. Among multiple strategies proposed to circumvent this challenge, intranasal delivery route has sparked great interest for brain targeting in the past decades. The aim of this study was to apply scientometric method to estimate the current status and future trends of the field from a holistic perspective.

          Methods: All relevant publications during 1998–2020 were retrieved from the Web of Science Core Collection (SCIE, 1998-present). Two different scientometric software including VOS viewer and CiteSpace, and one online platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of journals, countries, institutes, authors, references and keywords.

          Results: A total of 2,928 documents, including 2,456 original articles and 472 reviews, were retrieved. Our analysis revealed a significant increasing trend in the total number of scientific publications over the past 2 decades ( R 2 = 0.98). The United States dominated the field, reflecting in the largest amount of publications (971), the highest H-index (99), and extensive international collaboration. Jamia Hamdard contributed to most publications. Frey WH and Illum L were key researchers with the highest number of publications and citations, respectively. The International Journal of Pharmaceutics was the most influential academic journal, and Pharmacology/Pharmacy and Neurosciences/Neurology were the hottest research categories in this field. Based on keywords occurrence analysis, four main topics were identified, and the current research focus of this field has shifted from cluster 4 (pathways and mechanisms of intranasal delivery) to cluster 2 (the study of nasal drug delivery systems), especially the nanostructured and nano-sized carrier systems. Keywords burst detection revealed that the research focus on oxidative stress, drug delivery, neuroinflammation, nanostructured lipid carrier, and formulation deserves our continued attention.

          Conclusion: To the authors’ knowledge, this is the first scientometric analysis regarding intranasal delivery research. This study has demonstrated a comprehensive knowledge map, development landscape and future directions of intranasal delivery research, which provides a practical and valuable reference for scholars and policymakers in this field.

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          Software survey: VOSviewer, a computer program for bibliometric mapping

          We present VOSviewer, a freely available computer program that we have developed for constructing and viewing bibliometric maps. Unlike most computer programs that are used for bibliometric mapping, VOSviewer pays special attention to the graphical representation of bibliometric maps. The functionality of VOSviewer is especially useful for displaying large bibliometric maps in an easy-to-interpret way. The paper consists of three parts. In the first part, an overview of VOSviewer’s functionality for displaying bibliometric maps is provided. In the second part, the technical implementation of specific parts of the program is discussed. Finally, in the third part, VOSviewer’s ability to handle large maps is demonstrated by using the program to construct and display a co-citation map of 5,000 major scientific journals.
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            An index to quantify an individual's scientific research output.

            I propose the index h, defined as the number of papers with citation number > or =h, as a useful index to characterize the scientific output of a researcher.
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              Exosomes as drug delivery vehicles for Parkinson's disease therapy.

              Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson's disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100-200nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                12 July 2021
                2021
                : 12
                : 717192
                Affiliations
                [ 1 ]Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
                [ 2 ]Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, China
                [ 3 ]Department of Ultrasound, Tianjin Huanhu Hospital, Tianjin, China
                [ 4 ]Department of Spine and Spinal Cord, Tianjin Huanhu Hospital, Tianjin, China
                Author notes

                Edited by: Márcio José De Abreu Marques Rodrigues, University of Beira Interior, Portugal

                Reviewed by: Franciska Erdő, Pázmány Péter Catholic University, Hungary

                Ravish J. Patel, Charotar University of Science and Technology, India

                *Correspondence: Hua Yan, yanhua20042007@ 123456sina.com ; Zhiming Sun, szhm618@ 123456163.com
                [†]

                These authors have contributed equally to this work

                This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology

                Article
                717192
                10.3389/fphar.2021.717192
                8311521
                34322030
                88c2b866-a44b-484b-bcd4-47d69304fd41
                Copyright © 2021 Wu, Zhou, Wang, Tong, Wang, Song, Xu, Liu, Yan and Sun.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 May 2021
                : 29 June 2021
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                scientometric,intranasal drug delivery,blood-brain barrier,cns disorders,citespace,vos viewer

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