\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"7882",leadTitle:null,fullTitle:"Behavioral Pharmacology - From Basic to Clinical Research",title:"Behavioral Pharmacology",subtitle:"From Basic to Clinical Research",reviewType:"peer-reviewed",abstract:"Behavioral pharmacology studies the biological bases of behavior and the pharmacological effects of natural or synthetic drugs through behavioral analysis, with the identification of substances that could contribute to improvement of the quality of life for humans. Through behavioral pharmacology, it is possible to generate knowledge about pharmacological bases that influence the normal or altered behavior from a multidisciplinary point of view, and which includes diverse areas of science. The purpose of this book “Behavioral Pharmacology- From Basic to Clinical Research” is to show some of the advances in the identification of pharmacological properties of natural and synthetic molecules that may be used in the development of pharmacological therapies destined for the treatment of illness and disorders that affect the wellness of humans.",isbn:"978-1-78985-680-4",printIsbn:"978-1-78985-679-8",pdfIsbn:"978-1-83880-574-6",doi:"10.5772/intechopen.77701",price:119,priceEur:129,priceUsd:155,slug:"behavioral-pharmacology-from-basic-to-clinical-research",numberOfPages:168,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"39b4b6a6a15f5131f34bfcb11b050523",bookSignature:"Juan Francisco Rodríguez-Landa and Jonathan Cueto-Escobedo",publishedDate:"October 14th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7882.jpg",numberOfDownloads:4433,numberOfWosCitations:1,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:3,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 7th 2019",dateEndSecondStepPublish:"September 16th 2019",dateEndThirdStepPublish:"November 15th 2019",dateEndFourthStepPublish:"February 3rd 2020",dateEndFifthStepPublish:"April 3rd 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"45702",title:"Dr.",name:"Juan Francisco",middleName:null,surname:"Rodríguez-Landa",slug:"juan-francisco-rodriguez-landa",fullName:"Juan Francisco Rodríguez-Landa",profilePictureURL:"https://mts.intechopen.com/storage/users/45702/images/system/45702.png",biography:"Juan Francisco Rodríguez-Landa received his doctorate degree in Psychology (Behavioral Neuroscience) from the Universidad Nacional Autónoma de México (UNAM). He is a full-time researcher at the Laboratory of Neuropharmacology, Institute of Neuroethology, Universidad Veracruzana. He is a lecturer in Neuropsychopharmacology and belongs to the National System of Investigators (SNI 2) and Mexican Academy of Sciences. His research interests include the effects of neurosteroids and natural products on anxiety, depression, and neuronal activity in some brain structures related to anxiety and depression disorders. He has published multiple specialized scientific papers, book chapters, and books. He is an expert journal peer reviewer and active member of the European Behavioral Pharmacology Society, International Society for Neuroethology, and Mexican Society of Physiological Sciences, among others.",institutionString:"Universidad Veracruzana",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Universidad Veracruzana",institutionURL:null,country:{name:"Mexico"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"199455",title:"Dr.",name:"Jonathan",middleName:null,surname:"Cueto-Escobedo",slug:"jonathan-cueto-escobedo",fullName:"Jonathan Cueto-Escobedo",profilePictureURL:"https://mts.intechopen.com/storage/users/199455/images/system/199455.jpeg",biography:"Jonathan Cueto-Escobedo received his doctorate degree in Psychology (Behavioral Neuroscience) from the Universidad Nacional Autónoma de México. He is currently a researcher at the Institute of Health Sciences, Universidad Veracruzana and a member of the National System of Investigators (SNI I). His research interests include experimental models of anxiety and depression, neurobiology of behavior, particularly addiction and food intake as a reward with a translational perspective. He has published 10 book chapters and 13 scientific papers and made more than 20 presentations at international conferences. He has also published several works of science divulgation. He has lectured at several universities in México, including the University of Xalapa, University of Veracruz, University of Guadalajara, University of Tlaxcala, and Universidad Nacional Autónoma de México.",institutionString:"Institute of Neuroetology, University of Veracruz",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1063",title:"Psychopharmacology",slug:"psychopharmacology"}],chapters:[{id:"72210",title:"Introductory Chapter: Behavioral Pharmacology - From Basic to Clinical Research",doi:"10.5772/intechopen.92446",slug:"introductory-chapter-behavioral-pharmacology-from-basic-to-clinical-research",totalDownloads:487,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Juan Francisco Rodríguez-Landa and Jonathan Cueto-Escobedo",downloadPdfUrl:"/chapter/pdf-download/72210",previewPdfUrl:"/chapter/pdf-preview/72210",authors:[{id:"45702",title:"Dr.",name:"Juan Francisco",surname:"Rodríguez-Landa",slug:"juan-francisco-rodriguez-landa",fullName:"Juan Francisco Rodríguez-Landa"}],corrections:null},{id:"73245",title:"New Developments in Behavioral Pharmacology",doi:"10.5772/intechopen.93700",slug:"new-developments-in-behavioral-pharmacology",totalDownloads:621,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Behavioral pharmacology research has been a cornerstone in the understanding of the processes that underlie the behavior of living organisms as well as the biological basis of the behavioral, emotional, and cognitive disorders that affect humans. The findings in this area have helped to explore the potential therapeutic effects of several substances for the treatment of the mentioned disorders. The present chapter brings an extremely brief introduction to this vast area. First, we try to put in context behavioral pharmacology and its relevance and then show some brief examples of how this discipline has developed over the years. Second, we review the concept of a “research model” in preclinical behavioral pharmacology, given the importance of animal models and tests in this area, followed by a brief review of the recent advances using zebra fish as a valuable tool of research. Third, more specific examples are aborded, such as the findings on sleep disorders and those related to sexual hormones and menopause.",signatures:"Jonathan Cueto-Escobedo, Fabio García-García, Caio Maximino and Juan Francisco Rodríguez-Landa",downloadPdfUrl:"/chapter/pdf-download/73245",previewPdfUrl:"/chapter/pdf-preview/73245",authors:[{id:"45702",title:"Dr.",name:"Juan Francisco",surname:"Rodríguez-Landa",slug:"juan-francisco-rodriguez-landa",fullName:"Juan Francisco Rodríguez-Landa"},{id:"199455",title:"Dr.",name:"Jonathan",surname:"Cueto-Escobedo",slug:"jonathan-cueto-escobedo",fullName:"Jonathan Cueto-Escobedo"},{id:"108955",title:"Dr.",name:"Fabio",surname:"García-García",slug:"fabio-garcia-garcia",fullName:"Fabio García-García"},{id:"329483",title:"Ph.D.",name:"Caio",surname:"Maximino",slug:"caio-maximino",fullName:"Caio Maximino"}],corrections:null},{id:"70466",title:"Berry Supplementation and Their Beneficial Effects on Some Central Nervous System Disorders",doi:"10.5772/intechopen.90428",slug:"berry-supplementation-and-their-beneficial-effects-on-some-central-nervous-system-disorders",totalDownloads:812,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter is based in the compilation and analysis of different in vitro, preclinical, and clinical studies, which explored the potential beneficial bioactivity of supplementation with berries on some alterations in the central nervous system (CNS). The last section of the chapter describes the possible mechanisms of action of polyphenols, anthocyanins, and other compounds present in berries as well as their relationship with anxiety, depression, and Alzheimer’s (AD) and Parkinson’s diseases (PD) and their implication in the prevention of cognitive decline and senescence motor functions. Electronic databases as Springer, PubMed, Scopus, and Elsevier were used. Papers were selected by topic specially those related with berries, year of publication, and authors. The present chapter evidenced the potential health effect as neuroprotector of different berries and their bioactive compounds mainly flavonoids, polyphenols, and anthocyanins, on diseases such as anxiety, depression, and Alzheimer’s and Parkinson’s diseases. In conclusion, for human nutrition berry fruit supplementation might be an excellent source of antioxidant and alternative for prevention and reduction of symptoms in diseases such as anxiety, depression, Alzheimer’s, and Parkinson’s.",signatures:"Fernández-Demeneghi Rafael, Vargas-Moreno Isidro, Acosta-Mesa Héctor-Gabriel, Puga-Olguín Abraham, Campos-Uscanga Yolanda, Romo-González Tania, Guzmán-Gerónimo Rosa-Isela, Patraca-Camacho Lorena and Herrera-Meza Socorro",downloadPdfUrl:"/chapter/pdf-download/70466",previewPdfUrl:"/chapter/pdf-preview/70466",authors:[{id:"79033",title:"Dr.",name:"Héctor-Gabriel",surname:"Acosta-Mesa",slug:"hector-gabriel-acosta-mesa",fullName:"Héctor-Gabriel Acosta-Mesa"},{id:"174651",title:"Dr.",name:"Abraham",surname:"Puga-Olguín",slug:"abraham-puga-olguin",fullName:"Abraham Puga-Olguín"},{id:"188935",title:"Dr.",name:"Tania",surname:"Romo-Gonzalez",slug:"tania-romo-gonzalez",fullName:"Tania Romo-Gonzalez"},{id:"195746",title:"Prof.",name:"Rosa",surname:"Guzmán-Gerónimo",slug:"rosa-guzman-geronimo",fullName:"Rosa Guzmán-Gerónimo"},{id:"307885",title:"Ph.D.",name:"Socorro",surname:"Herrera-Meza",slug:"socorro-herrera-meza",fullName:"Socorro Herrera-Meza"},{id:"307887",title:"Dr.",name:"Rafael",surname:"Fernández-Demeneghi",slug:"rafael-fernandez-demeneghi",fullName:"Rafael Fernández-Demeneghi"},{id:"307888",title:"Dr.",name:"Isidro",surname:"Vargas-Moreno",slug:"isidro-vargas-moreno",fullName:"Isidro Vargas-Moreno"},{id:"307889",title:"Prof.",name:"Yolanda",surname:"Campos-Uscanga",slug:"yolanda-campos-uscanga",fullName:"Yolanda Campos-Uscanga"},{id:"311157",title:"Ms.",name:"Lorena-Guadalupe",surname:"Patraca-Camacho",slug:"lorena-guadalupe-patraca-camacho",fullName:"Lorena-Guadalupe Patraca-Camacho"}],corrections:null},{id:"71478",title:"Pharmaceutical and Botanical Management of Pain Associated with Psychopathology: A Narrative Review",doi:"10.5772/intechopen.91154",slug:"pharmaceutical-and-botanical-management-of-pain-associated-with-psychopathology-a-narrative-review",totalDownloads:706,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Generally, pain can be described as an unpleasant sensory or emotional experience associated with tissue damage. Chronic pain has become a public health problem because among 35 and 75% of the world population has shown the symptom. In particular, neuropathic pain has shown high comorbidity disorders such as anxiety and depression. Conventional therapies for treating pain include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, tricyclic antidepressants, anticonvulsants, and opioids, which usually cause some side effects such as gastritis, headache, liver and kidney toxicity, and drug dependence. Conventional pharmaceuticals also tend to be expensive, and they cannot be easily afforded in developing countries, which have led to the use of natural products as an alternative treatment. In this chapter, we reviewed the current research of natural products for pain treatment. We also describe preclinical studies that assess the effect of some natural products on pain therapy, phytochemistry research, toxicity, adverse effects, and biosecurity. We also describe how conventional pain is managed and the possible use of compounds obtained from vegetable species for pain treatment.",signatures:"Minerva Hernández Lozano, Marcos Fernando Ocaña Sánchez, Rosa Virginia García Rodríguez, Van Dan Castro Gerónimo, Libna Sulem Gallardo Beatriz, Ibrahim Guillermo Castro Torres, María Gabriela Alcántara López, Julio César González Ortiz, Gabriela Josefina Mendoza Rangel and Tania Monserrat Camacho Márquez",downloadPdfUrl:"/chapter/pdf-download/71478",previewPdfUrl:"/chapter/pdf-preview/71478",authors:[{id:"309190",title:"MSc.",name:"Marcos Fernando",surname:"Ocaña-Sanchez",slug:"marcos-fernando-ocana-sanchez",fullName:"Marcos Fernando Ocaña-Sanchez"},{id:"309238",title:"Dr.",name:"Minerva",surname:"Hernández Lozano",slug:"minerva-hernandez-lozano",fullName:"Minerva Hernández Lozano"},{id:"309240",title:"Dr.",name:"Ibrahim",surname:"Castro Torres",slug:"ibrahim-castro-torres",fullName:"Ibrahim Castro Torres"},{id:"309241",title:"BSc.",name:"Van Dan",surname:"Castro Gerónimo",slug:"van-dan-castro-geronimo",fullName:"Van Dan Castro Gerónimo"},{id:"309423",title:"Dr.",name:"Rosa Virginia",surname:"García Rodríguez",slug:"rosa-virginia-garcia-rodriguez",fullName:"Rosa Virginia García Rodríguez"},{id:"309424",title:"MSc.",name:"Libna Sulem",surname:"Gallardo Beatriz",slug:"libna-sulem-gallardo-beatriz",fullName:"Libna Sulem Gallardo Beatriz"},{id:"309425",title:"Dr.",name:"María Gabriela",surname:"Alcántara López",slug:"maria-gabriela-alcantara-lopez",fullName:"María Gabriela Alcántara López"},{id:"309426",title:"Dr.",name:"Julio César",surname:"González Ortiz",slug:"julio-cesar-gonzalez-ortiz",fullName:"Julio César González Ortiz"},{id:"309427",title:"BSc.",name:"Tania Monserrat",surname:"Camacho Márquez",slug:"tania-monserrat-camacho-marquez",fullName:"Tania Monserrat Camacho Márquez"},{id:"311285",title:"Dr.",name:"Gabriela Josefina",surname:"Mendoza Rangel",slug:"gabriela-josefina-mendoza-rangel",fullName:"Gabriela Josefina Mendoza Rangel"}],corrections:null},{id:"70960",title:"Neuropharmacology of Secondary Metabolites from Plants with Anxiolytic and Antidepressant Properties",doi:"10.5772/intechopen.90919",slug:"neuropharmacology-of-secondary-metabolites-from-plants-with-anxiolytic-and-antidepressant-properties",totalDownloads:890,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Depression and anxiety currently rank as the second and fifth most common causes worldwide of years lived with disability-a reality that has intensified the search for new treatments. There are many studies of herbal extracts and secondary metabolites from plants used in traditional medicine due to their antidepressant and anxiolytic properties. Clinical and preclinical studies about some of the mechanisms of action of metabolites like alkaloids, terpenes, flavonoids, and sterols, among others, have documented effects similar to those produced by clinically effective drugs. These metabolites have shown anxiolytic and antidepressant effects in various experimental models of anxiety by interacting with γ-aminobutyric acid subtype A receptors (GABAA-receptors) and by stimulating the serotonergic, noradrenergic, and dopaminergic neurotransmitter systems. These pharmacological effects can be attributed to plant metabolites that share structural similarities with monoamines, which allow them to bind to receptors. The objective of this chapter is to summarize the various mechanisms of action that have been identified in secondary metabolites with anxiolytic and antidepressant properties. Terpenes, alkaloids, flavonoids, and sterols can interact at different levels of the neurotransmission systems involved in the neurobiology of anxiety and depression, suggesting their potential for treating these mental illnesses.",signatures:"Rosa Isela García-Ríos, Armando Mora-Pérez, Ana Raquel Ramos-Molina and Cesar Soria-Fregozo",downloadPdfUrl:"/chapter/pdf-download/70960",previewPdfUrl:"/chapter/pdf-preview/70960",authors:[{id:"174653",title:"Dr.",name:"Rosa Isela",surname:"García-Ríos",slug:"rosa-isela-garcia-rios",fullName:"Rosa Isela García-Ríos"},{id:"174654",title:"Dr.",name:"Cesar",surname:"Soria-Fregozo",slug:"cesar-soria-fregozo",fullName:"Cesar Soria-Fregozo"},{id:"244518",title:"M.Sc.",name:"Ana",surname:"Ramos-Molina",slug:"ana-ramos-molina",fullName:"Ana Ramos-Molina"},{id:"306469",title:"Dr.",name:"Armando",surname:"Mora- Pérez",slug:"armando-mora-perez",fullName:"Armando Mora- Pérez"}],corrections:null},{id:"70505",title:"Neuropharmacology of Anxiety Disorders at Young Age: A Perspective from Preclinical Research",doi:"10.5772/intechopen.90486",slug:"neuropharmacology-of-anxiety-disorders-at-young-age-a-perspective-from-preclinical-research",totalDownloads:587,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Anxiety is one of the most common psychopathologies in the general population that often begin early in life; however, research on this disorder during early developmental stages has been poorly explored compared to adults. A better understanding of the anxiety disorder through childhood is essential to develop more effective treatments. This chapter provides a general overview of the usefulness of animal models of childhood anxiety and its neurobiological bases to discuss how the studies on animals meet the several criteria of validity to discover pathophysiological mechanisms of human disorders and new treatments for these conditions. The research methodology for this chapter consisted in using a thesaurus system such as Medical Subject Headings (MeSH) terms of the National Library of Medicine to find original articles in databases as PubMed or Web of Science about preclinical findings related to the neuropharmacology of anxiety before adulthood. The contribution of this chapter is to provide data from preclinical studies which are encouraged to a better comprehension of anxiety at young age.",signatures:"Gabriel Guillén-Ruiz, Blandina Bernal-Morales, César Soria-Fregozo, Emma Virginia Herrera-Huerta, Ana Karen Limón-Vázquez, Margarita Hernández-Mixteco and Abraham Puga-Olguín",downloadPdfUrl:"/chapter/pdf-download/70505",previewPdfUrl:"/chapter/pdf-preview/70505",authors:[{id:"174651",title:"Dr.",name:"Abraham",surname:"Puga-Olguín",slug:"abraham-puga-olguin",fullName:"Abraham Puga-Olguín"},{id:"174654",title:"Dr.",name:"Cesar",surname:"Soria-Fregozo",slug:"cesar-soria-fregozo",fullName:"Cesar Soria-Fregozo"},{id:"45701",title:"Dr.",name:"Blandina",surname:"Bernal-Morales",slug:"blandina-bernal-morales",fullName:"Blandina Bernal-Morales"},{id:"218681",title:"Dr.",name:"Gabriel",surname:"Guillén-Ruiz",slug:"gabriel-guillen-ruiz",fullName:"Gabriel Guillén-Ruiz"},{id:"306437",title:"Dr.",name:"Emma Virgina",surname:"Herrera-Huerta",slug:"emma-virgina-herrera-huerta",fullName:"Emma Virgina Herrera-Huerta"},{id:"306438",title:"MSc.",name:"Ana Karen",surname:"Limón-Vázquez",slug:"ana-karen-limon-vazquez",fullName:"Ana Karen Limón-Vázquez"},{id:"306439",title:"MSc.",name:"Margarita",surname:"Hernández-Mixteco",slug:"margarita-hernandez-mixteco",fullName:"Margarita Hernández-Mixteco"}],corrections:null},{id:"72041",title:"Comprehensive Attention with a Harm Reduction Perspective for Psychoactive Substances Consumers in a Third Level Hospital",doi:"10.5772/intechopen.91150",slug:"comprehensive-attention-with-a-harm-reduction-perspective-for-psychoactive-substances-consumers-in-a",totalDownloads:333,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The great problem of addictions during the last five decades has been investigated through the behavioral analysis of social determinants involving multiple risk factors of initiation and maintenance of legal and illegal substances consumption, as well as the search of protective factors that allow preventing and achieving abstinence of drug abuse. Currently there is no solution and we are at the crossroads of lacking comprehensive attention, since there are treatments focused only on achieving abstinence and do not pay attention to the physical consequences of substance consumption, such as: infectious and non-communicable diseases. It is important to treat the addictions problem with a holistic approach, which facilitates access to effective medical services, based on scientific evidence, applied to adherence to treatment and adapted to patient diagnosis. 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Reva",authors:[{id:"34440",title:"Dr.",name:"Oleg",middleName:null,surname:"Reva",fullName:"Oleg Reva",slug:"oleg-reva"},{id:"39708",title:"Mr.",name:"Oliver",middleName:null,surname:"Bezuidt",fullName:"Oliver Bezuidt",slug:"oliver-bezuidt"},{id:"39709",title:"Dr.",name:"Hamilton",middleName:null,surname:"Ganesan",fullName:"Hamilton Ganesan",slug:"hamilton-ganesan"},{id:"39710",title:"Mr.",name:"Phillip",middleName:null,surname:"Labuschange",fullName:"Phillip Labuschange",slug:"phillip-labuschange"},{id:"86235",title:"Mr.",name:"Warren",middleName:null,surname:"Emmett",fullName:"Warren Emmett",slug:"warren-emmett"},{id:"86238",title:"Mr.",name:"Rian",middleName:null,surname:"Pierneef",fullName:"Rian Pierneef",slug:"rian-pierneef"}]},{id:"20321",title:"On the Structural Characteristics of the Protein Active Sites and Their Relation to Thermal Fluctuations",slug:"on-the-structural-characteristics-of-the-protein-active-sites-and-their-relation-to-thermal-fluctuat",signatures:"Shao-Wei Huang and Jenn-Kang Hwang",authors:[{id:"35336",title:"Prof.",name:"Jenn-Kang",middleName:null,surname:"Hwang",fullName:"Jenn-Kang Hwang",slug:"jenn-kang-hwang"},{id:"48026",title:"Prof.",name:"Shao-Wei",middleName:null,surname:"Huang",fullName:"Shao-Wei Huang",slug:"shao-wei-huang"}]},{id:"20322",title:"Decomposition of Intramolecular Interactions Between Amino-Acids in Globular Proteins - A Consequence for Structural Classes of Proteins and Methods of Their Classification",slug:"decomposition-of-intramolecular-interactions-between-amino-acids-in-globular-proteins-a-consequence-",signatures:"Boris Fackovec and Jiri Vondrasek",authors:[{id:"38217",title:"Dr.",name:"Jiri",middleName:null,surname:"Vondrasek",fullName:"Jiri Vondrasek",slug:"jiri-vondrasek"},{id:"50346",title:"Mr",name:"Boris",middleName:null,surname:"Fackovec",fullName:"Boris Fackovec",slug:"boris-fackovec"}]},{id:"20323",title:"The Prediction and Analysis of Inter- and Intra-Species Protein-Protein Interaction",slug:"the-prediction-and-analysis-of-inter-and-intra-species-protein-protein-interaction",signatures:"Theresa Tsun-Hui Tsao, Chen-Hsiung Chan, Chi-Ying F. Huang and Sheng-An Lee",authors:[{id:"37527",title:"Dr.",name:"Sheng-An",middleName:null,surname:"Lee",fullName:"Sheng-An Lee",slug:"sheng-an-lee"},{id:"50910",title:"Dr.",name:"Chen-Hsiung",middleName:null,surname:"Chan",fullName:"Chen-Hsiung Chan",slug:"chen-hsiung-chan"},{id:"50911",title:"Prof.",name:"Chi-Ying F.",middleName:null,surname:"Huang",fullName:"Chi-Ying F. Huang",slug:"chi-ying-f.-huang"},{id:"50985",title:"Dr.",name:"Theresa Tsun-Hui",middleName:null,surname:"Tsao",fullName:"Theresa Tsun-Hui Tsao",slug:"theresa-tsun-hui-tsao"}]},{id:"20324",title:"Computational Prediction of Post-Translational Modification Sites in Proteins",slug:"computational-prediction-of-post-translational-modification-sites-in-proteins",signatures:"Yu Xue, Zexian Liu, Jun Cao and Jian Ren",authors:[{id:"31851",title:"Dr.",name:"Yu",middleName:null,surname:"Xue",fullName:"Yu Xue",slug:"yu-xue"},{id:"47639",title:"Mr",name:"Zexian",middleName:null,surname:"Liu",fullName:"Zexian Liu",slug:"zexian-liu"},{id:"47640",title:"Ms.",name:"Jun",middleName:null,surname:"Cao",fullName:"Jun Cao",slug:"jun-cao"},{id:"47643",title:"Prof.",name:"Jian",middleName:null,surname:"Ren",fullName:"Jian Ren",slug:"jian-ren"}]},{id:"20325",title:"Protein Networks: Generation, Structural Analysis and Exploitation",slug:"protein-networks-generation-structural-analysis-and-exploitation",signatures:"Enrico M. Bucci, Massimo Natale and Alice Poli",authors:[{id:"32246",title:"Dr",name:"Enrico",middleName:"M.",surname:"Bucci",fullName:"Enrico Bucci",slug:"enrico-bucci"},{id:"49231",title:"Dr.",name:"Massimo",middleName:null,surname:"Natale",fullName:"Massimo Natale",slug:"massimo-natale"},{id:"49232",title:"Dr.",name:"Alice",middleName:null,surname:"Poli",fullName:"Alice Poli",slug:"alice-poli"}]},{id:"20314",title:"Prediction and Analysis of Gene Regulatory Networks in Prokaryotic Genomes",slug:"prediction-and-analysis-of-gene-regulatory-networks-in-prokaryotic-genomes",signatures:"Richard Münch, Johannes Klein and Dieter Jahn",authors:[{id:"42008",title:"Prof.",name:"Dieter",middleName:null,surname:"Jahn",fullName:"Dieter Jahn",slug:"dieter-jahn"},{id:"49157",title:"Dr.",name:"Richard",middleName:null,surname:"Münch",fullName:"Richard Münch",slug:"richard-munch"},{id:"97182",title:"Dr.",name:"Johannes",middleName:null,surname:"Klein",fullName:"Johannes Klein",slug:"johannes-klein"}]},{id:"20315",title:"Mining Host-Pathogen Interactions",slug:"mining-host-pathogen-interactions",signatures:"Dmitry Korkin, Thanh Thieu, Sneha Joshi and Samantha Warren",authors:[{id:"45881",title:"Prof.",name:"Dmitry",middleName:null,surname:"Korkin",fullName:"Dmitry Korkin",slug:"dmitry-korkin"},{id:"63327",title:"Mr.",name:"Thanh",middleName:null,surname:"Thieu",fullName:"Thanh Thieu",slug:"thanh-thieu"},{id:"63328",title:"MSc",name:"Sneha",middleName:null,surname:"Joshi",fullName:"Sneha Joshi",slug:"sneha-joshi"},{id:"63329",title:"Mrs.",name:"Samantha",middleName:null,surname:"Warren",fullName:"Samantha Warren",slug:"samantha-warren"}]},{id:"20316",title:"Prediction of Novel Pathway Elements and Interactions Using Bayesian Networks",slug:"prediction-of-novel-pathway-elements-and-interactions-using-bayesian-networks",signatures:"Andrew P. Hodges, Peter Woolf and Yongqun He ξ",authors:[{id:"10751",title:"Prof.",name:"Yongqun",middleName:null,surname:"He",fullName:"Yongqun He",slug:"yongqun-he"},{id:"51200",title:"Dr.",name:"Andrew",middleName:null,surname:"Hodges",fullName:"Andrew Hodges",slug:"andrew-hodges"},{id:"51201",title:"Prof.",name:"Peter",middleName:null,surname:"Woolf",fullName:"Peter Woolf",slug:"peter-woolf"}]},{id:"20317",title:"MicroRNA Identification Based on Bioinformatics Approaches",slug:"microrna-identification-based-on-bioinformatics-approaches",signatures:"Malik Yousef, Naim Najami and Walid Khaleifa",authors:[{id:"48306",title:"Dr.",name:"Malik",middleName:null,surname:"Yousef",fullName:"Malik Yousef",slug:"malik-yousef"},{id:"48307",title:"Dr.",name:"Waleedd",middleName:null,surname:"Khalifa",fullName:"Waleedd Khalifa",slug:"waleedd-khalifa"},{id:"114762",title:"Dr",name:"Naim",middleName:null,surname:"Najami",fullName:"Naim Najami",slug:"naim-najami"}]},{id:"20318",title:"Motif Discovery with Compact Approaches - Design and Applications",slug:"motif-discovery-with-compact-approaches-design-and-applications",signatures:"Cinzia Pizzi",authors:[{id:"49149",title:"Dr.",name:"Cinzia",middleName:null,surname:"Pizzi",fullName:"Cinzia Pizzi",slug:"cinzia-pizzi"}]},{id:"20309",title:"Data Mining Pubmed Using Natural Language Processing to Generate the β-Catenin Biological Association Network",slug:"data-mining-pubmed-using-natural-language-processing-to-generate-the-catenin-biological-association-",signatures:"Fengming Lan, Xiao Yue, Lei Han, Peiyu Pu and Chunsheng Kang",authors:[{id:"32217",title:"Prof.",name:"Chunsheng",middleName:null,surname:"Kang",fullName:"Chunsheng Kang",slug:"chunsheng-kang"},{id:"46409",title:"Dr.",name:"Peiyu",middleName:null,surname:"Pu",fullName:"Peiyu Pu",slug:"peiyu-pu"},{id:"48460",title:"MSc.",name:"Xiao",middleName:null,surname:"Yue",fullName:"Xiao Yue",slug:"xiao-yue"},{id:"48461",title:"MSc.",name:"Fengming",middleName:null,surname:"Lan",fullName:"Fengming Lan",slug:"fengming-lan"}]},{id:"20310",title:"In Silico Identification of Plant-Derived Antimicrobial Peptides",slug:"in-silico-identification-of-plant-derived-antimicrobial-peptides",signatures:"Maria Clara Pestana-Calsa and Tercilio Calsa Jr.",authors:[{id:"42085",title:"Dr.",name:"Tercilio",middleName:null,surname:"Calsa Jr",fullName:"Tercilio Calsa Jr",slug:"tercilio-calsa-jr"},{id:"114941",title:"Dr.",name:"Maria Clara",middleName:null,surname:"Pestana-Calsa",fullName:"Maria Clara Pestana-Calsa",slug:"maria-clara-pestana-calsa"}]},{id:"20311",title:"Mining Effector Proteins in Phytopathogenic Fungi",slug:"mining-effector-proteins-in-phytopathogenic-fungi",signatures:"Li Cheng-yun and Yang Jing",authors:[{id:"50639",title:"Prof.",name:"Chengyun",middleName:null,surname:"Li",fullName:"Chengyun Li",slug:"chengyun-li"},{id:"50640",title:"Dr.",name:"Jing",middleName:null,surname:"Yang",fullName:"Jing Yang",slug:"jing-yang"}]},{id:"20312",title:"Immuno-Modulatory Effects of Phytomedicines Evaluated Using Omics Approaches",slug:"immuno-modulatory-effects-of-phytomedicines-evaluated-using-omics-approaches",signatures:"Shu-Yi Yin and Ning-Sun Yang",authors:[{id:"41256",title:"Prof.",name:"Ning-Sun",middleName:null,surname:"Yang",fullName:"Ning-Sun Yang",slug:"ning-sun-yang"},{id:"53084",title:"Mr.",name:"Shu-Yi",middleName:null,surname:"Yin",fullName:"Shu-Yi Yin",slug:"shu-yi-yin"},{id:"53085",title:"Dr.",name:"Kandan",middleName:null,surname:"Aravindaram",fullName:"Kandan Aravindaram",slug:"kandan-aravindaram"}]},{id:"20313",title:"High Content and Throughput Drug Discovery",slug:"high-content-and-throughput-drug-discovery",signatures:"Quin Wills",authors:[{id:"44195",title:"Dr.",name:"Quin",middleName:null,surname:"Wills",fullName:"Quin Wills",slug:"quin-wills"}]}]}],publishedBooks:[{type:"book",id:"260",title:"Systems and Computational Biology",subtitle:"Molecular and Cellular Experimental Systems",isOpenForSubmission:!1,hash:"701901030f1fc71b5712857445649f26",slug:"systems-and-computational-biology-molecular-and-cellular-experimental-systems",bookSignature:"Ning-Sun Yang",coverURL:"https://cdn.intechopen.com/books/images_new/260.jpg",editedByType:"Edited by",editors:[{id:"41256",title:"Prof.",name:"Ning-Sun",surname:"Yang",slug:"ning-sun-yang",fullName:"Ning-Sun Yang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1405",title:"Systems and Computational Biology",subtitle:"Bioinformatics and Computational Modeling",isOpenForSubmission:!1,hash:"c648682f141815097872c4d82d47ee9b",slug:"systems-and-computational-biology-bioinformatics-and-computational-modeling",bookSignature:"Ning-Sun 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Yang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"74144",title:"A Novel Drug Delivery System Based on Nanoparticles of Magnetite Fe3O4 Embedded in an Auto Cross-Linked Chitosan",doi:"10.5772/intechopen.94873",slug:"a-novel-drug-delivery-system-based-on-nanoparticles-of-magnetite-fe-sub-3-sub-o-sub-4-sub-embedded-i",body:'Nowadays, the global increase in the number of people with chronic diseases as “cancer, diabetes, etc.” have affected the health and quality of life of many citizens around the world. For example, cancer is considered a public health problem because of its high incidence and mortality. The World Health Organization (WHO) estimates 27 million cases of cancer and 17 million deaths disease for the year 2030 [1]. Therefore, study on cancer treatment has attracted many scientists. Among therapies, cancer chemotherapy is widely used despite its disadvantages. Chemotherapy usually causes serious side effects because of the low selectivity of anti-cancer drugs, which affects not only cancer cells but also normal cells [2]. Thus, increasing attention is being paid to targeted drug delivery systems, which have been used to increase the efficiency of drug delivery to specific tissues and to decrease the associated side effects.
The most efficient solution is to use nanoparticles embedded in the hydrogel; this innovative-targeted drug delivery strategy involves coupling the drug to magnetic nanoparticles (NPs) that can be guided to the target using external magnetic fields [3]. Once they reach the target, the nanoparticles release the drugs under the influence of an alternating magnetic field [4]. Nanoparticle (NP) targeting has shown great potential for cancer drug delivery applications over the past decade. From nanoparticle targeting, magneto-particle have been widely studied because of their ability to target when an external magnetic field is applied [5].
An increasing population causes serious environmental pollution, waste production is also increasing and major proportion of by-products generated by contemporary food remains underused which may often contain precious substances. The crucial problem confronting by industries and society in food processing is the elimination of food waste. Chitin is an important natural resource and the world’s annual production of it is approximately 1010–1012 tons [6]. This latter is principally produced by mollusks, arthropods (crustaceans and insects) and fungi [7]. However, chitin and its derivatives have a high economic impact due to their numerous applications in the pharmaceutical [8], food [9, 10], cosmetics [11], textile [12], wastewater treatment and agricultural sectors [13].
In the past few decades, drug delivery systems (DDS) have been of great interest and resulted in many efforts to realize the effectiveness and targeted drug delivery tendency as well as to reduce the associated side effects [14]. However, DDS provide several advantages as compared to conventional dosages in terms of improved efficacy, reduced toxicity, improved patient compliance, and convenience [15]. Thus, the carriers used for drug release are generally biodegradable polymers which are extensively used for designing the control drug delivery systems [16].
On the other hand, with the rapid development of technology much attention has been given to use biopolymer based hydrogels in many applications including pharmaceuticals [17, 18], cosmetics [19], agriculture [20] and biotechnology [21, 22]. However, porous biomaterials fabricated from natural polymers “chitosan” were given significant attention for years. Chitosan is a unique natural cationic biopolymer produced by N-deacetylation of chitin and is the second most abundant natural polymer after cellulose [23]. Chitosan has been widely used in the biomedical field due to its superior properties including good biodegradability [24], biocompatibility [24], low toxicity [25, 26], mucoadhesive properties [27], antibacterial activity [28] and low cost [24, 29]. Chitosan is an excellent candidate for different applications particularly it has been employed in various FDA (Food and Drug Administration) approved biomedical applications. The -NH2 group of the (CS) chains is a pH-sensitive polymer with pKa around 6.5 due to variation of charge density at the pH range of 6–6.5, which is useful for wide range of pharmaceuticals applications. The pH value of the soluble-insoluble transition in the range 6–6.5 [30]. At pH levels beneath the pKa, high charge density of chitosan results in polyelectrolyte formation, in contrast at neutral pH, the low charge density of chitosan eases the intracellular release of biomolecules and contributes to its low cytotoxicity [31]. Chitosan has increasingly been used in the pharmaceutical field as it is one of the excellent choices for the Schiff’s base linkages to form an injectable hydrogel due to the nature of abundant amino groups on its backbone. Hydrogels from chitosan are usually prepared through physical interchain interaction or chemical reaction of the free amine groups with crosslinker agents (e.g. glutaraldehyde, glyoxal [32]). The disadvantage of these crosslinking agents, especially glutaraldehyde [33], benzaldehyde [34] and glyoxal is their toxicity to human tissues even at small traces [35], which has limited the use of chitosan hydrogels as scaffolds for drug delivery.
However, this paper discusses the recent trends in drug delivery systems (DDS) applications using macroscopic hydrogels. Hydrogel has received extensive attention due to its interconnected cross-linked porous hydrophilic polymer networks which can absorb large amounts of water or biological fluids. Additionally, hydrogels can be divided into three categories according to their size: macroscopic gels, nanogels (<200 nm), and microgels (0.5–10 μm). Hydrogels are promising, fashionable, intelligent and “smart” drug delivery vehicles that meet specific requirements for targeting drugs to specific sites and controlling drug release. The hydrogel-based drug carrier loaded with 5-fluorouracil (5-FU) drug for an up to 36 days sustained delivery has been studied by Xueyun Chen et al. [36].
Hydrogels are trendy, promising, intelligent and ‘smart’ drug delivery vehicles have become a great search field for targeting drugs to the specific sites and controlling drug release. Among several hardware platforms, ferrogels (FG) have a high potential for use in drug delivery. Ferrogels (FG) are consisting mainly of a polymer matrix embedded with magnetic micro and nano-particles (Fe3O4) [37, 38, 39]. Upon the application of an external magnetic field, the polymer matrix of the ferrogel can deform due to the magnetic force generated by the embedded magnetic particles, which would allow actuation and magnetically driven drug release on demand. The main advantage of ferrogels is that a larger quantity of drug can be loaded, compared to that transported by simple magnetic dispersion nanoparticles.
Ferrogel (FG) are typically prepared by incorporating magnetic particles into hydrogels [40]. Magnetic nanoparticles (Fe3O4) shown in Figure 1, have attracted much attention in the last few years as carriers for drug delivery systems. The potential use of nanoparticles as drug carriers has been presented in recent years as a major challenge, as nanoparticles have been designed to improve pharmacological and therapeutic effects in terms of reducing their toxic side effects. Besides, magnetite (Fe3O4) is considered as an important type of magnetic material with cubic inverse spinel structure. This property makes it very interesting because of its wide field of use, including magnetic recording, ferrofluid [41], catalyst [42] and some biomedical applications like magnetic resonance imaging (MRI) [43], bio separation [44], in addition to drug delivery system and therapeutic hyperthermia as well, to treat cancer and tumors [45]. Several methods have been developed recently for preparing magnetic nanoparticles, such as co-precipitation [46], sol–gel [47], solvothermal [48], sonochemical and chemical vapor deposition phase (CVD) [49]. Among these methods, co-precipitation is considered as the simplest, most efficient, and most economic method.
Model of crystal structure of magnetite (Fe3O4) and spherical Fe3O4 nanoparticles.
Ferrogels characterized by the presence of magnetic particles incorporated in polymer gels, are the subject of extensive research due to those magnetic particles and magnetic fields which have an extended application and clinical acceptance [50, 51]. Recent studies have shown controlled release of many drugs from ferrogels subject to magnetic fields [52, 53]. Ferrogels (FG) have made also injectable and biodegradable. However, typical drug delivery ferrogels have a disadvantage due to the cross-linking agent toxicity, which limits the macroporous biomaterials synthesis [37].
There are only a few reports in the literature on the synthesis of Fe3O4 by co-precipitation method. In this paper, a macroporous ferrogel which is sensitive to magnetic field was studied. Furthermore, we are probably the first scientific team that reports the preparation of novel hydrogels and ferrogels based on chitosan and oxidized chitosan as cross-linking agent embedded Fe3O4/drug (5-FU, caffeine and ascorbic acid). Figure 2 shows the magnetic drug delivery system under the influence of external magnetic field. The kinetics and in-vitro drug release profile of the drugs were studied in PBS pH (7.4) buffered solution at 37°C.
Schematic representation of magnetic drug delivery system under the influence of external magnetic field.
Chitosan (in powder form was prepared in our laboratory from exoskeletons of shrimp waste and purified, with degree of deacetylation >90% was determined by conductimetric titration), iron (II) sulfate heptahydrate (FeSO4.7H2O, sigma-Aldrich), iron (III) chloride (FeCl3.6H2O, Sigma-Aldrich), Caffeine (sigma-Aldrich), 5-Fluorouracil (sigma-Aldrich), Ascorbic acid (Fluka), Sodium metaperiodate (NaIO4, sigma-Aldrich), Hydrochloric acid (sigma-Aldrich), Ethylene glycol (sigma-Aldrich), Acetic acid (sigma-Aldrich), Sodium bicarbonate (Panreac), Sodium hydroxide (Sigma-Aldrich).
Oxidized chitosan (Figure 3) was prepared according to a previously reported method [54, 55]. The purified chitosan (1 g) ([GlcN] = 5.34 mM) was dispersed in 50 ml Hydrochloric acid solution HCl (10−3 M) at pH ranging from 4 to 5, and kept under magnetic stirring at 4°C for 30 min. Then 1 ml aqueous solution of sodium periodate 0.534 mM, P0 = 0.1 (P0 = moles of NaIO4 x moles of GlcN) was added to the mixture. The reaction system was covered with aluminum foil to prevent photo induced decomposition of periodate ion. The reaction lasted for 30 min at 4°C and it was interrupted by the addition of 1 ml ethylene glycol to inactivate any unreacted periodate in a molar ratio of 1:1. The oxidized derivative was washed by distilled water for 5 h and the dry product was obtained by freeze-drying.
Schematic representation of reaction between chitosan (CS) by sodium periodate.
The procedure for preparation of the hydrogel was as follows: chitosan (0.1 g) was dispersed in 10 ml of (1% acetic acid) at pH = 4.8 in an ice bath under magnetic stirring until a clear solution was obtained. Afterwards, the drug (5-FU 10 mg, Caffeine 10 mg or Ascorbic acid 10 mg) was added into the solution and gently stirred until the complete dissolution for 30 min. The oxidized chitosan (60 mg) was added to the solution of chitosan soluble drug under continuous stirring to facilitate crosslinking between amino of chitosan (NH2) and aldehyde groups of chitosan (OCS). Then the 6% (w/v) NaHCO3 solution was slowly added to the solution in an ice bath under magnetic stirring to get homogeneous mixture at pH = 7 [56], and a transparent gel was obtained as shown in Figure 4. The hydrogel was washed with ethanol, and filtered to remove traces of unreacted reagents.
Schematic representation of the chemical (CS)/(OCS) cross-linking mechanism and the formation of the hydrogel.
According to the previous work, magnetite (Fe3O4) nanoparticles were synthesized by chemical co-precipitation method. Magnetic Fe3O4 NPs were synthesized by dissolving 50 mL of FeCl3.6H2O and 25 mL of FeSO4.7H2O in 350 mL of distilled water under nitrogen atmosphere under vigorous stirring. Upon addition of (35 ml) NaOH, the pH was adjusted to about 10, the solution turned black, indicating the formation of magnetite nanoparticles. Further stirring is continued for 1 h to uniformly disperse the magnetic nanoparticles. After raising the reaction temperature to 80°C. Then, a formed black precipitate was collected with an external magnet, washed several times with ethanol and distilled water, and dried in vacuum at 60°C. The entire reaction is given by the equation as shown in Figure 5.
Representation of superparamagnetic magnetite nanoparticles synthesis technique.
Firstly, chitosan solution was prepared by dissolving 0.1 g chitosan (CS) in 10 mL acetic acid solution (1%). 50 mg iron oxide nanoparticles were mixed with chitosan solution and stirred for 2 h at 40°C to give chitosan coated magnetic nanoparticles (CS-Fe3O4). Then, the drug (5-FU 10 mg, Caffeine 10 mg or Ascorbic acid 10 mg) was added into the solution (CS-Fe3O4) and gently stirred for 30 min. 60 mg of oxidized chitosan (OCS) was added as crosslinking agent and were mixed with (CS-Fe3O4) solution. The reaction mixture was stirred at 0°C for 3 hours. The pH of the solution was adjusted to pH = 7 with 6% (w/v) NaHCO3. The product (CS-Fe3O4-OCS) was washed with deionized water. Figure 6 shows a representation of the prepared drug delivery ferrogel.
Representation of superparamagnetic drug delivery hydrogel.
Fourier transform infrared (FTIR) spectra of the chitosan, oxidized chitosan, CS/OCS hydrogel, CS/drug/OCS lyophilized hydrogel, Fe3O4 NPs and the freeze-dried CS/Fe3O4/OCS ferrogel were obtained from discs containing 2.0 mg dry sample in approximately 198 mg potassium bromide (KBr). The measurements were recorded by a Perkin–Elmer FTIR spectrophotometer at the resolution of 4 cm−1 in the wave number region 400–4000 cm−1.
The thermal properties of lyophilized hydrogel, pure chitosan, oxidized chitosan, Fe3O4 NPs and CS/Fe3O4/OCS lyophilized ferrogel were investigated by thermogravimetric analysis (TGA). Samples were placed in the balance system and heated from 40 to 800°C at a heating rate of 10°C/min using a TA Instruments TGA (Q500) device.
The saturation magnetization of Fe3O4 NPs, CS-Fe3O4-OCS ferrogel was measured by vibrating sample magnetometer VSM (SQUID model MPMS XL 7) from Quantum at room temperature between magnetic fields of −14,000 (Oe) to 14,000 (Oe).
The chitosan-based hydrogels cross-linked with oxidized chitosan was frozen at −75°C for 24 h and then lyophilized (by Alpha 1–2 LDplus) for 48 h. The lyophilized sample was obtained and then examined by a scanning electron microscopy (SEM) (Mini SEM Hirox SH-4000).
Freeze-dried CS/OCS hydrogel were immersed in phosphate-buffered saline (PBS) at 37°C (pH = 1.2, pH = 5.8 and pH = 7.4). The samples were weighed before being put into PBS (W0). After the vial was sealed and held at 37°C for 24 h, and the excess solution on the surface of the hydrogels was quickly absorbed with filter paper [55]. The equilibrium-swelling ratio (SR) was calculated using the following equation:
where, Wd is the weight of dry hydrogel after lyophilization and Ws is the weight of swollen hydrogel.
(5-FU, caffeine or ascorbic acid) was selected and used as a model drug in the release experiments. In vitro drug release test was performed in a phosphate buffer solution PBS (pH 7.4 at 37°C) under shaking. The hydrogels and ferrogels (m = 1.14 g) (3 cm x 4 cm) were placed in a cartouche before immersing in 1000 mL of phosphate-buffered saline (PBS). At predetermined time intervals, 5 mL of release medium was withdrawn. Then 5 mL of fresh buffer was added to the original to maintain the total volume. The drug release was determined by UV–Vis spectrophotometry at λmax (5-Fluorouracil (266 nm), caffeine (273 nm) and ascorbic acid (265 nm)). The concentration of the active ingredient in the (PBS, pH = 7.4 at 37°C) has been achieved from the calibration curve, and the amount of drug released at time t (Mt) was calculated by accumulating the total active ingredient release up to that time. In vitro drug release tests were performed in triplicate (n = 3). There are a few steps, which mainly control drug release phenomena from the polymer matrix, dissolution of the drug, liquid penetration into the matrix and diffusion of the drug from the drug encapsulated in the matrix. In order to understand the release kinetics and the mechanism of the active ingredient release, release kinetics data obtained in vitro using ferrogels and hydrogels are fitted with kinetics model. The release data are best fitted with the Korsmeyer−Peppas (KP) model. The (KP) model deal with Eq [57]:
where “Mt” is the amount of drug released at time (t), “M0” is the maximal amount of the drug released at maximum interval. It is interesting to note that three drugs (5-FU, caffeine and ascorbic acid) in hydrogels exhibit a Fickian nature of drug diffusion. However, the interaction of the drug molecules with the matrix play an important role in the drug release kinetics occurring through a diffusion mechanism.
The experimental data are expressed as the mean values of at least three replicates ± standard deviation (SD). The results were analyzed and showed usage Kaleida graph.
The concept of this study is depicted in (Figure 7). Oxidized chitosan (OCS) was prepared following a well-known method where chitosan is oxidized with sodium periodate (NaIO4). Oxidization of chitosan created multiple aldehyde groups all along the polymeric chain using the method described in literature [54, 58]. The hydrogels and ferrogels (magnetic Fe3O4 embedded in novel hydrogel) were prepared by crosslinking chitosan (CS) with oxidized chitosan (OCS). The crosslinking of hydrogel and ferrogel was achieved by (–C=N-) bonds of Schiff-base reaction. Our results indicate that the process synthesis of the hydrogel and ferrogel was embedded with three drugs (5-FU, caffeine and ascorbic acid) has successfully loaded in the carrier polymeric. The schematic representation of smart ferrogel “magnetic hydrogel” was shown in (Figure 7).
Schematic representation of (CS-Fe3O4-OCS) ferrogel.
The Figure 8 shows the procedure for preparation of the hydrogel and a photograph of (CS-drug-OCS) hydrogel.
Schematic representation of the synthesis process of CS/drug/OCS hydrogel.
The IR spectrum of CS, OCS, (CS/OCS) and (CS/drug/OCS) lyophilized hydrogel are listed in (Figures 9 and 10) and major functional moieties are labeled with wavenumbers was recorded in the region of 4000–40 cm−1. The FTIR spectrum of pure chitosan (Figure 9(a)) shows wide band around 3450 cm−1 corresponding to amine N–H symmetrical vibration and H bonded O–H group. The peak observed between 3400 and 3700 cm−1 corresponding to combination of the band O-H, NH2 intra and intermolecular hydrogen bonding. The peaks at 2920 and 2320 cm−1 are assigned to the symmetric and asymmetric may be attributed to –CH vibrations of carbohydrate ring [59]. The bands at 1650 cm−1 and 1545 cm−1 may be attributed to C=O stretching (amide I vibration) and N-H bending (–NH2 bending of amide II) in amide group, respectively and 1390 cm−1 (N–H stretching or C–N bond stretching vibrations, amide III vibration) [60]. The peak observed at 1050 cm−1 has the contribution to the symmetric stretching of C–O–C groups. The absorption peaks in the range 900–1200 cm−1 are due to the antisymmetric C–O stretching of saccharide structure of chitosan. In order to understand the oxidation of oxidized chitosan (OCS), the FTIR spectra results for (OCS) in (Figure 9(b)) verified successful oxidation, while a new absorption peak appeared around 1725 cm−1 [55], which was assigned to an aldehyde group (-C=O) bond, indicating that the CS has been successfully oxidized by the NaIO4 [61]. Furthermore, the peak (Figure 9(c) at 1637 cm−1 caused by C=O and C=N is reduced significantly. These differences indicate that the aldehyde groups of OCS reacted with the amino groups of CS to generate a Schiff base”imine” [62]. FTIR analysis was performed (Figure 9(d)) exhibits the IR spectra of the prepared nanoparticles. The spectrum of Fe3O4 magnetic nanoparticles shows the formation of two strong absorption bands between 636 cm−1 and 592 cm−1. Furthermore, the band at 592 cm−1 was confirmed as the Fe-O stretching vibration of tetrahedral sites of spinel structure. The absorption bands at 459 cm−1, assigned to tetrahedral and octahedral sites, peaks at 3400 cm−1 due to the O-H stretching model adsorbed on the surface of the Fe3O4 nanoparticles [63].
FTIR spectra of (a) chitosan, (b) oxidized chitosan, (c) CS/OCS lyophilized hydrogel, (d) Fe3O4 NP.
FTIR spectra of (a) CS/a.AS/OCS lyophilized hydrogel, (b) CS/CAF/OCS lyophilized hydrogel; (c) CS/5FU/OCS lyophilized hydrogel.
For the spectra of three drugs (5-FU, caffeine and ascorbic acid) loaded (CS/OCS) in hydrogels (Figure 10); exhibited the characteristic absorption of imine stretching vibration (-C=N–) at 1637 cm−1 [54, 64], suggests that the coupling reaction was occurred between –CHO of OCS and –NH2 of CS.
The measurements of the magnetic field-dependence of the magnetization of the uncoated and coated magnetite nanoparticles at 25°C are presented in (Figure 11). The plots indicate that both samples exhibit superparamagnetic behavior with zero remanence and coercivity. (Figure 11) shows the magnetic curves as a function of applied field at room temperature obtained for Fe3O4 and CS-Fe3O4-OCS ferrogel, respectively. The magnetization saturations were found to be 60.57 emu/g for Fe3O4, 17.25 emu/g for CS-Fe3O4-OCS ferrogel [65]. The magnetization value decreased after coating due to the existence of oxidized chitosan and chitosan, which formed polymerized multilayers. It can be concluded that the Ms. value of CS/Fe3O4/OCS ferrogel is less than the Fe3O4 (NPs) that can be attributed to the creation of a non-magnetic polymer layer around Fe3O4 (NPs) in the hydrogel [66]. Taking into account the magnetic properties of the prepared by ferrogel, it may be able to deliver the drug to the target area in the presence of an external magnetic field.
The magnetic hysteresis loops for Fe3O4 NPs and CS@Fe3O4@OCS hydrogel measured by SQUID at room temperature.
A perfect injectable hydrogel must have pores in the range of 50–100 μm and a high degree of interconnectivity to facilitate nutrient and oxygen transport, as well as cell adhesion and migration. By using SEM, we studied the pore size distribution in hydrogels (Figure 12). In this study, morphology of freeze-dried hydrogel (CS/OCS) were observed with scanning electron microscope (SEM). As can be seen in (Figure 12), the (CS/OCS) lyophilized hydrogel had continuous and porous structures with interconnecting pores, pores diameter ranging from several tens to several thousands of micrometers [55]. Moreover, the more crosslinking between amino group and aldehyde group, the diameter of the pores are decreased and the compactness of pores increased. The micrographs of CS/OCS hydrogel it was clearly observed that the hydrogel had a three-dimensional porous structure, which was beneficial for drug delivery systems.
Micrographs of chitosan cross-linked oxidized chitosan hydrogel at low and high magnification.
To evaluate the thermal stability of the chitosan (CS) oxidized chitosan (OCS) and (CS/OCS) lyophilized hydrogel, TGA thermograms were obtained as shown in (Figure 13). The TGA of pure chitosan shows two-stage weight loss in the range 40 to 750°C (Figure 13), it is clear that chitosan started to degrade at 40–130°C with 8% weight is due to the loss of water molecules. Initial decomposition around 130°C for pure chitosan can be attributed to the strong water adsorptive nature of chitosan. The second stage of degradation occurred at 340°C and continued up to 460°C [67]. There was 38.43% weight loss occurring in the second stage due to degradation of pure chitosan biopolymer and the temperature at which maximum degradation observed was 274.74°C. At the end of 750°C, the total weight loss of sample was 100% [54, 67]. TGA of oxidized chitosan (OCS) showed two steps of degradation (Figure 13), the first stage ranges between 40 and 130°C and shows about 8.2% loss in weight corresponded to water release for the initial step. The second stage decomposition was observed from 300°C and continued up to 460°C, during this time there was 39% weight loss due to the degradation of chitosan. At the end of 700°C, the total weight loss of sample was 90% [10, 54]. For CS/OCS lyophilized hydrogel, the degradation starts at a lower temperature compared to chitosan and oxidized chitosan (Figure 13). For the CS/OCS hydrogel, shows two-stage weight loss in three stages. The first stages of degradation takes place from 40 to 160°C with a weight loss of 13% could be due to the loss of both the loosely bound water and tightly bound water [68]. The free water and hydrogen-bonded water are released at a temperature between 40 and 100°C. The hydrogel contains many hydrophilic groups that retain water more tightly in the hydrogel skeleton by polar interaction. As a result, it is harder to lose. Thus, this tightly bound water is released in the temperature region 100–156°C. The second stage of hydrogel degradation started between 160° C and 385° C with a 41% weight loss. The three-stages of degradation biopolymers, at the end of 700°C, the total weight loss of sample was 90%. This phase of the weight loss mainly could be caused by a series of thermal and oxidative decomposition in the process including dehydration of the sugar cycle, degradation, N-deacetylation of the molecular chain of the chitosan cracking unit and vaporization and removal of volatile products. It can be concluded the TGA curve shows at about 222°C. This is probably due to the formation of (-C=N-) and this proves that biopolymer-based Schiff base is thermally less stable.
TGA graphs of chitosan (CS), oxidized chitosan (OCS) and (CS/OCS) lyophilized hydrogel.
The TGA curves of uncoated Fe3O4 and the lyophilized ferrogel (CS-Fe3O4-OCS) are shown in Figure 14. For uncoated Fe3O4 NPs (Figure 14(a)), the TGA curve showed that the weight loss over the temperature range 40–750°C was about 2.2%. Hence, this weight loss is related to removal of the physically adsorbed water and/or hydroxyl groups on the surface of Fe3O4 nanoparticles. For coated nanoparticles Fe3O4. Similarly, the weight curve of CS/Fe3O4/OCS (Figure 14(b)) showed a progressive decrease of 85%. This is due to the degradation of the polymer and hydrogen-bound water in the temperature range of 40–166°C, which forms the polysaccharide structure of OCS and CS. In addition, a uniform and steady decrease in weight loss at 166–630°C is CS/Fe3O4/OCS was observed. This may be partly attributed to the degradation and decomposition of organic skeletal structure, amino groups, and other functional groups. By comparing the curves of CS/Fe3O4/OCS and Fe3O4, it was observed that Fe3O4 particles are wrapped into CS and OCS can enhance the thermal stability of the whole system. A temperature of 630°C or higher, the remaining material was carbonized completely. The indicated that chitosan and oxidized chitosan coated Fe3O4 successfully and penetrated deeply into in the matrix CS/OCS.
TGA curves for a) uncoated Fe3O4 b) CS-Fe3O4-OCS lyophilized ferrogel.
To investigate the pH dependent swelling behavior of the CS/OCS hydrogels for drug delivery, PBS with (pH = 1.2; pH = 5.8 and pH = 7.4) at T = 37°C were used to simulate the physiological medium and were used for testing swelling of the hydrogels. The results of the equilibrium-swelling ratio are presented in (Figure 15). The CS/OCS hydrogels showed large differences in swelling behavior at different pH values. The pKa value of the D-glucosamine residue in chitosan was approximately 6.2 to 7.0. Therefore, the amino groups in the chitosan were protonated and positively charged in acidic PBS (pH = 1.2 and pH = 5.8), and the electrostatic repulsion between positively charged -NH3+ groups would lead to swelling of the hydrogels. The % equilibrium swelling values were found to be higher at pH = 1.2, than at pH = 7.4. This can be explained by protonation of the unreacted NH2 groups of chitosan at acidic pH, leading to dissociation of the hydrogen bonding involving the amino groups, and thus facilitating the entry of the solvent into the material. The swelling process of hydrogels involves the ionization [69]. Furthermore, the Schiff base bonds between -NH2 and -CHO as a cross-linker became weak in PBS (pH = 7.4 at 37°C); the swelling ratio of CS/OCS was 350%, resulting in swelling of the hydrogel. Therefore, the CS/OCS hydrogel in PBS (pH = 1.2 at 37°C) exhibited the largest swelling ratio of 670%; the swelling ratio (pH = 5.8 at 37°C) was 509%. The decreased swelling ratio occurred due to increased crosslinking density in the hydrogels. Meanwhile, the equilibrium swelling ratios of the hydrogels in a pH = 7.4 solution dramatically decreased. This is because hydrogels exhibited pH-responsive swelling behavior, and the hydrogels showed a much higher swelling ratio in an acidic medium than that in a pH 7.4 medium.
% Swelling of CS/OCS hydrogel in buffer solutions of pH = 1,2, pH = 5,8 and pH = 7,4 at T = 37°C.
The model drugs (5-FU, caffeine and ascorbic acid) was encapsulated in the hydrogel matrix used for the release kinetics in PBS (pH = 7.4 at 37°C) are depicted in (Figure 16). The purpose here was to study whether the release of the drug trapped in the hydrogels, as well as by the simple diffusion. In a system, where drug is entrapped in a biodegradable matrix, the release rate depends on three parameters: the size of the drug molecule, the drug solubility (soluble-sparingly soluble-insoluble), the cross-linking density and the degradation rate. The ability of the chitosan-imine-oxidized chitosan hydrogels to act as matrix for controlled release was investigated in vitro by monitoring the release profile of the (5-FU, caffeine and ascorbic acid) three-model drug from system in phosphate buffer of physiological pH (7.4), at the human body temperature of 37°C (Figure 16). In order to study the release behavior of 5-FU, caffeine, ascorbic acid incorporated in the chitosan-based hydrogel cross-linked by oxidized chitosan, they were incubated in release media (phosphate buffer pH = 7.4 at 37°C) and evaluated by UV spectrophotometry. (Figure 16) shows release profiles of 5-FU, caffeine and ascorbic acid up to 26 h of incubation period. As shown in (Figure 16), the chitosan hydrogels showed an initial burst release of 5-FU, caffeine and ascorbic acid over a period of 3 h for all incubation media, which was of the order of (5 -FU “52%”, caffeine “43%” and ascorbic acid “60%”). This initial rapid release, characterized by a “burst effect», because certain quantities of 5-FU, caffeine and ascorbic acid were localized on the surface of the hydrogels by adsorption which could be released easily by diffusion. After 3h the release percentages of (5-FU “86%”, caffeine “89%” and ascorbic acid “91%”), respectively [70]. The remaining part of the drug can be trapped in hydrogels because the amino functions of chitosan can enter into the Schiff reaction with the aldehyde groups of oxidized chitosan. Indeed, the hydrogel contained large pore size, which is beneficial for the diffusion of the drug, this initial bursting effect, a slower sustained and controlled release occurred throughout the incubation period and the amount of release. The release profiles confirmed that the (5-FU, caffeine and ascorbic acid) drugs were encapsulated in hydrogels.
In vitro release of 5-FU, caffeine and ascorbic acid embedded in hydrogels (pH = 7,4 at 37°C). Values reported are an average of n = 3 ± standard deviation.
As shown in Figure 17, magneto-hydrogel showed an initial burst release of (5-FU, caffeine and ascorbic acid) in a period of 5 h, which was in the range of (37%, 34%, and 42%). The initial burst phase is caused by drug adsorbed on the surface of the nanoparticles Fe3O4 embedded in hydrogel. The release kinetics at pH = 7.4 at 37°C within 45 h clearly indicated that Fe3O4 embedded in hydrogel influenced drugs release. At pH = 7.4 at 37°C, about (95%, 93% and 97%) amounts of 5-FU, caffeine and ascorbic acid were release after 45 h, respectively. Due to the slower swelling rate of nanotransporters in solution, the rate of drug release is also slower. It is well known that there are a large number of amino and hydroxyl groups on the surface of chitosan molecules, which provide functional groups and favorable characteristics for biological molecules. In PBS (pH = 7.4 at 37°C), amino groups of chitosan mainly attach to the surface of the nanoparticles, so as to reduce the surface voids and render the pore blockage, lower penetration, and thus slow down the release rate of the drug [36]. However, due to the magnetic orientation role of MNPs, magnetic nano-drug carriers could be transported by applying an external magnetic field and maintain drug concentration for extended periods. Such rapid transport and slow release of the nanocarriers to the target site may be desirable for many biomedical applications, minimizing drug leakage to undesirable sites and reducing the risk of heart attack due to high dose in a short period of time. These results clearly illustrated that the chitosan hydrogel containing Fe3O4 resulted in a barrier system for the sustained release of 5-Fu, caffeine and ascorbic acid. We speculate that this barrier structure would block the drug loss in the early burst release, which is benefit to reduce the toxic side effects.
Cumulative release profiles of 5-FU-gel, caffeine-gel, ascorbic acid-gel with external magnetic field. Values reported are an average of n = 3 ± standard deviation.
Many conclusions can be made from the present work, the ferrogels (FG) are cross-linked polymer networks containing magnetic nanoparticles: a) magnetic magnetite (Fe3O4) were synthesized successfully by chemical co-precipitation and has been confirmed using FT-IR, VSM analysis, TGA. The advantage of the co-precipitation method are low cost, rapidity, ease, reproducibility and high-yield synthesis. b) The hydrogel was formulated by cross-linking chitosan (CS) and oxidized chitosan (OCS) via the Schiff-base (-C=N-) reaction. Obviously, these results indicate that this exhibit non-toxic, biodegradable, good injectability, less expensive and respect the environment, quick gelation time, in vitro pH-dependent equilibrated swelling ratios, interconnected porosity. c) Magneto-responsive hydrogels are typically prepared by incorporating magnetic particles into hydrogels and has been confirmed using (FT-IR), (TGA), (VSM) analysis at room temperature. d) The role of Fe3O4 embedded in hydrogel, which allows reducing the surface voids and rendering the pore blockage, lower penetration, and thus slowing down the release rate of the drug. e) A 5-Fluorouracil (5-FU), caffeine and ascorbic acid release tests were used to demonstrate the excellent in vitro drug release behavior of these hydrogels and ferrogels. However, all these results indicate that this type of biomaterial based on chitosan with oxidized chitosan in the presence of the three drugs with different solubility for the preparation of hydrogels effective for the controlled release of the drug. Compared to other hydrogels based on chitosan, the present study brings to the attention of researchers a novel strategy to design a non-toxic and biodegradable matrix for drug delivery systems, by the simple use of appropriate oxidized chitosan without incorporating any crosslinking agents. This design expands the variety of hydrogel matrices, guiding additional efforts in the development of the new ideas for pharmaceuticals applications. As a perspective and future challenges, we will test this type of ferrogels for cancer treatment by hyperthermia.
IntechOpen publishes different types of publications
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\n\nEdited Volumes can be comprised of different types of chapters:
\n\nRESEARCH CHAPTER – A research chapter reports the results of original research thus contributing to the body of knowledge in a particular area of study.
\n\nREVIEW CHAPTER – A review chapter analyzes or examines research previously published by other scientists, rather than reporting new findings thus summarizing the current state of understanding on a topic.
\n\nCASE STUDY – A case study involves an in-depth, and detailed examination of a particular topic.
\n\nPERSPECTIVE CHAPTER – A perspective chapter offers a new point of view on existing problems, fundamental concepts, or common opinions on a specific topic. Perspective chapters can propose or support new hypotheses, or discuss the significance of newly achieved innovations. Perspective chapters can focus on current advances and future directions on a topic and include both original data and personal opinion.
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\n\nMonographs is a self-contained work on a particular subject, or an aspect of it, written by one or more authors. Monographs usually have between 130 and 500 pages.
\n\nTYPES OF MONOGRAPHS:
\n\nSingle or multiple author manuscript
\n\nCompacts provide a mid-length publishing format that bridges the gap between journal articles, book chapters, and monographs, and cover content across all scientific disciplines.
\n\nCompacts are the preferred publishing option for brief research reports on new topics, in-depth case studies, dissertations, or essays exploring new ideas, issues, or broader topics on the research subject. Compacts usually have between 50 and 130 pages.
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. 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Ovarian cancers are heterogenous cancers where each subtype possesses a varied morphology and biologic behavior. Accumulating evidence has identified each of these subtypes characterized with specific pathways activated in each along with specific gene alterations. For example, high-grade serous ovarian cancer is characterized by universal TP53 mutation, mucinous ovarian cancer with KRAS mutation and clear cell or endometrioid ovarian cancers with ARID1A mutations. With the current focus of molecular-targeted therapies for cancer, such druggable markers serve as excellent targets for precision therapy and combination therapy. This chapter, provides an overview of the critical molecular pathways activated in the ovarian cancer subtypes with its druggable targets studied in ovarian cancer. We also highlight the implications of miRNAs in chemoresistance and sensitivity in the regulation of ovarian cancer.",book:{id:"10342",slug:"ovarian-cancer-updates-in-tumour-biology-and-therapeutics",title:"Ovarian Cancer",fullTitle:"Ovarian Cancer - Updates in Tumour Biology and Therapeutics"},signatures:"Febina Ravindran and Bibha Choudhary",authors:[{id:"334121",title:"Prof.",name:"Bibha",middleName:null,surname:"Choudhary",slug:"bibha-choudhary",fullName:"Bibha Choudhary"},{id:"335007",title:"Dr.",name:"Febina",middleName:null,surname:"Ravindran",slug:"febina-ravindran",fullName:"Febina Ravindran"}]},{id:"42501",title:"Implication of Clear Cell and Mucinous Histology",slug:"implication-of-clear-cell-and-mucinous-histology",totalDownloads:2332,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"3449",slug:"ovarian-cancer-a-clinical-and-translational-update",title:"Ovarian Cancer",fullTitle:"Ovarian Cancer - A Clinical and Translational Update"},signatures:"Jun Naniwa, Hiroaki Itamochi and Junzo Kigawa",authors:[{id:"158925",title:"Prof.",name:"Junzo",middleName:null,surname:"Kigawa",slug:"junzo-kigawa",fullName:"Junzo Kigawa"}]},{id:"74781",title:"The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer",slug:"the-anti-cancer-effects-of-anti-parasite-drug-ivermectin-in-ovarian-cancer",totalDownloads:853,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Ivermectin is an old, common, and classic anti-parasite drug, which has been found to have a broad-spectrum anti-cancer effect on multiple human cancers. This chapter will focus on the anti-cancer effects of ivermectin on ovarian cancer. First, ivermectin was found to suppress cell proliferation and growth, block cell cycle progression, and promote cell apoptosis in ovarian cancer. Second, drug pathway network, qRT-PCR, and immunoaffinity blot analyses found that ivermectin acts through molecular networks to target the key molecules in energy metabolism pathways, including PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in oxidative phosphorylation, and MCT1 and MCT4 in lactate shuttle, to inhibit ovarian cancer growth. Third, the integrative analysis of TCGA transcriptomics and mitochondrial proteomics in ovarian cancer revealed that 16 survival-related lncRNAs were mediated by ivermectin, SILAC quantitative proteomics analysis revealed that ivermectin extensively inhibited the expressions of RNA-binding protein EIF4A3 and 116 EIF4A3-interacted genes including those key molecules in energy metabolism pathways, and also those lncRNAs regulated EIF4A3-mRNA axes. Thus, ivermectin mediated lncRNA-EIF4A3-mRNA axes in ovarian cancer to exert its anticancer capability. Further, lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565), which is significantly associated with overall survival and clinicopathologic characteristics in ovarian cancer patients. These ivermectin-related molecular pattern alterations benefit for prognostic assessment and personalized drug therapy toward 3P medicine practice in ovarian cancer.",book:{id:"10342",slug:"ovarian-cancer-updates-in-tumour-biology-and-therapeutics",title:"Ovarian Cancer",fullTitle:"Ovarian Cancer - Updates in Tumour Biology and Therapeutics"},signatures:"Xianquan Zhan and Na Li",authors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan"},{id:"438269",title:"Dr.",name:"Na",middleName:null,surname:"Li",slug:"na-li",fullName:"Na Li"}]},{id:"43345",title:"Surgical Treatment of Ovarian Cancer",slug:"surgical-treatment-of-ovarian-cancer",totalDownloads:2948,totalCrossrefCites:1,totalDimensionsCites:3,abstract:null,book:{id:"3449",slug:"ovarian-cancer-a-clinical-and-translational-update",title:"Ovarian Cancer",fullTitle:"Ovarian Cancer - A Clinical and Translational Update"},signatures:"Lucas Minig, M. 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A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. 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He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). 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She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}}]},{type:"book",id:"7144",title:"Veterinary Anatomy and Physiology",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7144.jpg",slug:"veterinary-anatomy-and-physiology",publishedDate:"March 13th 2019",editedByType:"Edited by",bookSignature:"Catrin Sian Rutland and Valentina Kubale",hash:"75cdacb570e0e6d15a5f6e69640d87c9",volumeInSeries:2,fullTitle:"Veterinary Anatomy and Physiology",editors:[{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}}]},{type:"book",id:"8524",title:"Lactation in Farm Animals",subtitle:"Biology, Physiological Basis, Nutritional Requirements, and Modelization",coverURL:"https://cdn.intechopen.com/books/images_new/8524.jpg",slug:"lactation-in-farm-animals-biology-physiological-basis-nutritional-requirements-and-modelization",publishedDate:"January 22nd 2020",editedByType:"Edited by",bookSignature:"Naceur M'Hamdi",hash:"2aa2a9a0ec13040bbf0455e34625504e",volumeInSeries:3,fullTitle:"Lactation in Farm Animals - Biology, Physiological Basis, Nutritional Requirements, and Modelization",editors:[{id:"73376",title:"Dr.",name:"Naceur",middleName:null,surname:"M'Hamdi",slug:"naceur-m'hamdi",fullName:"Naceur M'Hamdi",profilePictureURL:"https://mts.intechopen.com/storage/users/73376/images/system/73376.jpg",biography:"Naceur M’HAMDI is Associate Professor at the National Agronomic Institute of Tunisia, University of Carthage. He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. 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He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"95",type:"subseries",title:"Urban Planning and Environmental Management",keywords:"Circular economy, Contingency planning and response to disasters, Ecosystem services, Integrated urban water management, Nature-based solutions, Sustainable urban development, Urban green spaces",scope:"