Relationship between degree of deacetylation of chitosan and their water solubility [11].
\\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:"8592",leadTitle:null,fullTitle:"Mesoporous Materials - Properties and Applications",title:"Mesoporous Materials",subtitle:"Properties and Applications",reviewType:"peer-reviewed",abstract:"The basic theme of this book is to understand the fundamentals and importance of porous functional materials, their properties, and significant applications like solar cells, batteries, photovoltaics, energy conversions, and mesoporous materials. This book covers the fundamentals of mesoporous materials, and various methods of synthesis, properties, and applications in different sectors.",isbn:"978-1-83880-650-7",printIsbn:"978-1-83880-649-1",pdfIsbn:"978-1-83880-687-3",doi:"10.5772/intechopen.79068",price:119,priceEur:129,priceUsd:155,slug:"mesoporous-materials-properties-and-applications",numberOfPages:130,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"9af59f637c67eec81a23db27d63c1353",bookSignature:"Manjunath Krishnappa",publishedDate:"May 29th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8592.jpg",numberOfDownloads:7160,numberOfWosCitations:9,numberOfCrossrefCitations:10,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:21,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:40,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 13th 2018",dateEndSecondStepPublish:"August 29th 2018",dateEndThirdStepPublish:"October 28th 2018",dateEndFourthStepPublish:"January 16th 2019",dateEndFifthStepPublish:"March 17th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"202044",title:"Dr.",name:"Manjunath",middleName:null,surname:"Krishnappa",slug:"manjunath-krishnappa",fullName:"Manjunath Krishnappa",profilePictureURL:"https://mts.intechopen.com/storage/users/202044/images/system/202044.jpeg",biography:"Krishnappa Manjunath received masters degree from the Sri Venkateshwara University, Tirupathi. He received Ph.D. from Jain University, India in Chemistry under the guidance of Prof. T. Ramakrishnappa in 2016. During his Ph.D., he was awarded a prestigious ‘CNPq-TWAS’ fellowship in 2014 for 1-year internship and worked with Prof. Jairton Dupont, FRS at Laboratory of Molecular Catalysis, UFRGS, Brazil. In 2016, he joined at International Centre for Materials Science, JNCASR, Bangalore where he is currently working as Research Associate with Bharat Ratna Prof. C. N. R. Rao, FRS. His research interests mainly focus on ‘Investigations on aliovalent anion substitution in inorganic materials and their applications for water splitting reactions to generate hydrogen’. He authored more than 30 papers, mainly concerning advanced functional materials and nanomaterials for photocatalysis.",institutionString:"Jawaharlal Nehru Centre for Advanced Scientific Research",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Jawaharlal Nehru Centre for Advanced Scientific Research",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"156",title:"Composite Materials",slug:"materials-science-composite-materials"}],chapters:[{id:"65758",title:"Synthesis and Characterizations of Titanium Tungstosilicate and Tungstophosphate Mesoporous Materials",doi:"10.5772/intechopen.82405",slug:"synthesis-and-characterizations-of-titanium-tungstosilicate-and-tungstophosphate-mesoporous-material",totalDownloads:918,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The work reports a development approach for the synthesis of novel multi-components mesoporous materials of titanium tungstate (meso-TiW) titanium tungstosilicate (meso-TiWSi) and tungstophosphate (meso-TiWP) mixed oxides that have high surface area and ordered mesoporous structures at nanometer length scale. Using the solvent evaporation-induced self-assembly (EISA) new oxides of bi- and tri-component of meso-TiW, meso-TiWSi and meso-TiWP oxides with different compositions and porosity were achieved. The physicochemical properties of the mesoporous oxides were characterized by X-ray diffraction, BET surface area analyzer, scanning, and transmission electron microscopes. Subject to the oxide composition, the obtained meso-TiW, meso-TiWSi and meso-TiWP exhibits high surface area, ordered 2D hexagonal mesostructured with order channels extended over a large area. The produced meso-TiW, meso-TiWSi, and meso-TiWP adsorbents exhibit good adsorption efficiency for the removal of Pb(II), Cd(II) and Hg(II) ions from water solution due to the presence of high surface area and accessibility of surface active sites. The adsorption efficiency of these mesoporous oxide reaches up to 95% and is found to be dependent contact time and adsorbents dose. The synthesis strategy is particularly advantageous for the production of new complex (multi-component) inorganic mesoporous materials that might have an application in the field of environmental, catalysis or energy storage and production.",signatures:"Mohamed A. Ghanem, Abdullah M. Al-Mayouf and Mabrook S. Amer",downloadPdfUrl:"/chapter/pdf-download/65758",previewPdfUrl:"/chapter/pdf-preview/65758",authors:[{id:"277689",title:"Prof.",name:"Mohamed",surname:"Ghanem",slug:"mohamed-ghanem",fullName:"Mohamed Ghanem"},{id:"277698",title:"Prof.",name:"Abdullah M.",surname:"Al-Mayouf",slug:"abdullah-m.-al-mayouf",fullName:"Abdullah M. Al-Mayouf"},{id:"277700",title:"Mr.",name:"Mabrook S.",surname:"Amer",slug:"mabrook-s.-amer",fullName:"Mabrook S. Amer"}],corrections:null},{id:"65289",title:"Mesoporous Materials Prepared Using Cashew Nut Shell Liquid and Castor Oil as Surfactants",doi:"10.5772/intechopen.83695",slug:"mesoporous-materials-prepared-using-cashew-nut-shell-liquid-and-castor-oil-as-surfactants",totalDownloads:935,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Preparation of useful materials using renewable resources, which are not in competition with food production is of particular importance in the current efforts to replace non-renewable resources. One example of a potential renewable resource, which is attracting the attention of researchers in the preparation of useful materials is cashew nut shell liquid (CNSL). CNSL which is a by-product of cashew processing factories, is a mixture of four potential compounds, namely anacardic acid, cardanol, cardol and 2-methyl cardol. Among other potential applications, cashew nut shell liquid is a good template source for preparation of mesoporous materials. Heterogeneous catalysts prepared using CNSL templates are more efficient than those prepared using the commercially available templates. The pore sizes of mesoporous materials prepared using CNSL templates are large (up to 25 nm) enough to immobilize enzymes. Another renewable resource; castor oil, has also been reported to be a good template source for preparation of mesoporous materials. This chapter therefore is aimed at describing in detail the preparation, characterization and applications of mesoporous materials templated by cashew nut shell liquid and castor oil.",signatures:"James Mgaya and Egid Mubofu",downloadPdfUrl:"/chapter/pdf-download/65289",previewPdfUrl:"/chapter/pdf-preview/65289",authors:[{id:"280637",title:"Dr.",name:"James",surname:"Mgaya",slug:"james-mgaya",fullName:"James Mgaya"},{id:"280756",title:"Prof.",name:"Egid",surname:"Mubofu",slug:"egid-mubofu",fullName:"Egid Mubofu"}],corrections:null},{id:"65810",title:"Synthesis of MCM-41/ZIF-67 Composite for Enhanced Adsorptive Removal of Methyl Orange in Aqueous Solution",doi:"10.5772/intechopen.84691",slug:"synthesis-of-mcm-41-zif-67-composite-for-enhanced-adsorptive-removal-of-methyl-orange-in-aqueous-sol",totalDownloads:821,totalCrossrefCites:4,totalDimensionsCites:9,hasAltmetrics:0,abstract:"ZIF-67 and MCM-41/ZIF-67 composites were successfully synthesized with water solvent at room temperature. The amounts of MCM-41 added during synthesis were varied at 2.5, 5 and 10 (%w/w) toward the amount of ZIF-67, and the obtained solids were denoted as MC (2.5)/ZIF-67, MC (5)/ZIF-67, and MC (10)/ZIF-67, respectively. The X-ray diffraction (XRD) patterns of ZIF-67 and the composites showed characteristic peaks at 2θ of 7.32, 10.36, 12.69, 14.66, and 16.40°, similar to that of reported ZIF-67. The Fourier transform infra-red (FT-IR) spectra of all solids showed absorption bands at the same wavenumbers as reported for ZIF-67. The results of surface morphology analysis using scanning electron microscope (SEM) have shown that ZIF-67 and the composites have a cube shape, which is characteristic for the ZIF-67 standard. N2 adsorption-desorption data showed that the specific surface area of ZIF-67 and MC (5)/ZIF-67 were 1079.2 and 1011.2 m2/g, respectively, lower than that of MC (10)/ZIF-67 (1250.6 m2/g). However, results of thermal gravimetric analysis (TGA) showed that the thermal stability of MC (10)/ZIF-67 reached 357°C, higher than that of ZIF-67 (325°C). Performance of the composites as adsorbent of methyl orange (MO) in aqueous solution showed that the MC (5)/ZIF-67 had the highest adsorption capacity of 167.635 mg/g, and followed the pseudosecond-order adsorption kinetics and Langmuir isothermal adsorption.",signatures:"Ratna Ediati, Pramita Elfianuar, Eko Santoso, Dety Oktavia Sulistiono and Muhammad Nadjib",downloadPdfUrl:"/chapter/pdf-download/65810",previewPdfUrl:"/chapter/pdf-preview/65810",authors:[{id:"264494",title:"Ph.D.",name:"Ratna",surname:"Ediati",slug:"ratna-ediati",fullName:"Ratna Ediati"},{id:"264495",title:"BSc.",name:"Pramita",surname:"Elfianuari",slug:"pramita-elfianuari",fullName:"Pramita Elfianuari"},{id:"272868",title:"MSc.",name:"Eko",surname:"Santoso",slug:"eko-santoso",fullName:"Eko Santoso"},{id:"272870",title:"BSc.",name:"Dety Oktavia",surname:"Sulistiono",slug:"dety-oktavia-sulistiono",fullName:"Dety Oktavia Sulistiono"},{id:"278972",title:"MSc.",name:"Muhammad",surname:"Nadjib",slug:"muhammad-nadjib",fullName:"Muhammad Nadjib"}],corrections:null},{id:"64611",title:"Synthesis, Properties, and Their Potential Application of Covalent Organic Frameworks (COFs)",doi:"10.5772/intechopen.82322",slug:"synthesis-properties-and-their-potential-application-of-covalent-organic-frameworks-cofs-",totalDownloads:2321,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Covalent organic frameworks (COFs) represent an emerging class of crystalline porous polymers, which are ingeniously assembled with organic building blocks through reversible covalent bonds. The well-defined crystalline porous structures, easy functional modification, high surface area, together with structural designability and diversity have offered the COFs superior potential in various applications, such as catalysis, gas adsorption and separation, and optoelectricity. Since the pioneer work of Omar Yaghi in 2005, this field has developed rapidly and attracted much attention from researchers with diverse expertise. In this chapter, we describe the basic design concepts, the recent synthetic advancements, and the frontiers of functional exploration in gas adsorption and storage. Special emphasis is placed on their potential application in heterogeneous catalysis field. Finally, the prospects of COFs and remaining issues in these fields are indicated.",signatures:"Lifeng Deng, Junfeng Zhang and Yanan Gao",downloadPdfUrl:"/chapter/pdf-download/64611",previewPdfUrl:"/chapter/pdf-preview/64611",authors:[{id:"171387",title:"Prof.",name:"Yanan",surname:"Gao",slug:"yanan-gao",fullName:"Yanan Gao"},{id:"265789",title:"BSc.",name:"Lifeng",surname:"Deng",slug:"lifeng-deng",fullName:"Lifeng Deng"},{id:"279899",title:"Mr.",name:"Junfeng",surname:"Zhang",slug:"junfeng-zhang",fullName:"Junfeng Zhang"}],corrections:null},{id:"65916",title:"Designed Mesoporous Materials toward Multifunctional Organic Silica Nanocomposites",doi:"10.5772/intechopen.84875",slug:"designed-mesoporous-materials-toward-multifunctional-organic-silica-nanocomposites",totalDownloads:1212,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Functionalized mesoporous silica materials (MSMs) using grafting (post-synthesis) and one-pot (co-condensation) synthesis methods of organic functional groups (periodic mesoporous organosilicas, PMOs) have been developed for many emerging applications. To improve the functions, designed MSMs have received particular attention using an organic motif as a molecule of surfactants for the template synthesis with a silica source in the sol-gel reaction. The resulting mesoporous silica materials can provide characteristic multifunctional nanocomposites consisting of a monomer for synthesizing polymer in the silicate nanochannels. Moreover, the nanocomposites can be also synthesized using a self-assembled organic motif for organizing one-dimensional structure in the silicate nanochannels. The resulting hybrid nanomaterials have been mainly reported to provide fluorescent properties. However, the utilization of phosphorescent nanocomposites for specific applications has not yet reported so far. By utilizing a self-assembled metal complex (organometallic), this chapter particularly highlights recent achievements of designed mesoporous silica materials for the fabrication of advanced luminescent nanostructures with phosphorescent properties where the potential applications will be discussed in detail for self-repairing and thermally resistive materials, metal ions sensors, template synthesis nanoparticles, and catalysts. Such better and novel performance can be only achieved using a designed template for the sol-gel synthesis of mesoporous silica nanocomposites.",signatures:"Hendrik O. Lintang and Leny Yuliati",downloadPdfUrl:"/chapter/pdf-download/65916",previewPdfUrl:"/chapter/pdf-preview/65916",authors:[{id:"264835",title:"Dr.",name:"Hendrik Oktendy",surname:"Lintang",slug:"hendrik-oktendy-lintang",fullName:"Hendrik Oktendy Lintang"},{id:"265656",title:"Dr.",name:"Leny",surname:"Yuliati",slug:"leny-yuliati",fullName:"Leny Yuliati"}],corrections:null},{id:"66506",title:"Mesoporous Materials for High-Performance Electrochemical Supercapacitors",doi:"10.5772/intechopen.85583",slug:"mesoporous-materials-for-high-performance-electrochemical-supercapacitors",totalDownloads:953,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Supercapacitors are very important kind of electrochemical energy storage devices. It differs from those of batteries and exhibit high power density. The energy storage in supercapacitors is influenced by many parameters like nature of electrode material, current collector, electrolyte, etc. among which most crucial is the morphology of the electrode. This makes most of the research works are targeting in designing suitable and high performing electrode materials by adopting new routes of synthesis, modifying the regular methods so on. Herein we discuss the fundamentals of supercapacitors, their design and approaches to obtain high-performance electrode materials.",signatures:"Ranganatha Sudhakar",downloadPdfUrl:"/chapter/pdf-download/66506",previewPdfUrl:"/chapter/pdf-preview/66506",authors:[{id:"271773",title:"Dr.",name:"Ranganatha",surname:"Sudhakar",slug:"ranganatha-sudhakar",fullName:"Ranganatha Sudhakar"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6513",title:"Cement Based Materials",subtitle:null,isOpenForSubmission:!1,hash:"7c92db3d5c64117861b425cb692b5695",slug:"cement-based-materials",bookSignature:"Hosam El-Din M. Saleh and Rehab O. Abdel Rahman",coverURL:"https://cdn.intechopen.com/books/images_new/6513.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. 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Kumavath and Pratap Deverapalli",dateSubmitted:"October 10th 2012",dateReviewed:"March 18th 2013",datePrePublished:null,datePublished:"October 2nd 2013",book:{id:"3547",title:"Applied Bioremediation",subtitle:"Active and Passive Approaches",fullTitle:"Applied Bioremediation - Active and Passive Approaches",slug:"applied-bioremediation-active-and-passive-approaches",publishedDate:"October 2nd 2013",bookSignature:"Yogesh B. 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Patil and Prakash Rao",coverURL:"https://cdn.intechopen.com/books/images_new/3547.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"164249",title:"Dr.",name:"Yogesh",middleName:"Bhagwan",surname:"Patil",slug:"yogesh-patil",fullName:"Yogesh Patil"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10979",leadTitle:null,title:"Parenting",subtitle:"Challenges of Child Rearing in a Changing Society",reviewType:"peer-reviewed",abstract:"Parenting is a lifelong task and parents are always remaining as a parent. Parenting in the present situation faces many challenges which need to be reviewed and understood with profuse equanimity and alacrity. This book tries to consider the process of parenting in different conditions such as during COVID-19 lockdown, in the refugee camps, and in different cultural structures and economic conditions. Situations that families face due to changing conditions such as global changes which cause lifestyles, immigration patterns, social conflicts, and raising children with developmental disabilities have been discussed. Topics such as professional concern with child care and education, gender roles and caregiving, and father’s involvement in parenting, have been covered in different chapters of the book.",isbn:"978-1-83969-973-3",printIsbn:"978-1-83969-972-6",pdfIsbn:"978-1-83969-974-0",doi:"10.5772/intechopen.95672",price:119,priceEur:129,priceUsd:155,slug:"parenting-challenges-of-child-rearing-in-a-changing-society",numberOfPages:252,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"6f345ebcf4fd61e73643c69063a12c7b",bookSignature:"Sayyed Ali Samadi",publishedDate:"May 4th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10979.jpg",keywords:null,numberOfDownloads:1336,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 2nd 2021",dateEndSecondStepPublish:"June 30th 2021",dateEndThirdStepPublish:"August 29th 2021",dateEndFourthStepPublish:"November 17th 2021",dateEndFifthStepPublish:"January 16th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a year",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:"A pioneering researcher in the field of establishing services for parents and children with Autism Spectrum Disorders (ASD) and other developmental disabilities in low and middle-income countries. Dr. Samadi obtained his doctorate at the University of Ulster, Northern Ireland, UK. He published 68 journal papers and edited 16 books.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"52145",title:"Dr.",name:"Sayyed Ali",middleName:null,surname:"Samadi",slug:"sayyed-ali-samadi",fullName:"Sayyed Ali Samadi",profilePictureURL:"https://mts.intechopen.com/storage/users/52145/images/system/52145.png",biography:"Dr. Sayyed Ali Samadi was born and raised in Mahabad the Kurdish city of Iran. He studied in Iran and the UK. He is an active researcher and an advocate in the field of developmental disabilities. His background is in Instructional Technology, child psychology, after which he received his Ph.D. in Intellectual and developmental disabilities. He has been acted as the advisor for establishing health and educational services for individuals with Autism Spectrum Disorders in Low- and middle-income countries. He has published over 40 research papers in international peer-review journals and published several books and book chapters in both Persian and English. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"74871",title:"Chitosan-Based Oral Drug Delivery System for Peptide, Protein and Vaccine Delivery",doi:"10.5772/intechopen.95771",slug:"chitosan-based-oral-drug-delivery-system-for-peptide-protein-and-vaccine-delivery",body:'The extent of drug bioavailability has been shown to be influenced by the route of drug administration. Oral drug route needs travelling through the continuous passageway of the GIT, which makes them susceptible to the harsh environment of GIT. Drugs intended for administration via this route can be formulated in a variety of dosage forms, such as tablets, capsules, solutions, and powders.
Due to its high patient compliance and ease of administration, the oral route of administration is preferred among other routes. Self-administration is possible with great compliance and reduced risk in developing systemic side effects, which is the major concern in the parenteral route [1]. Despite that, the oral delivery system approaches for certain drugs are challenging, especially the delivery of peptide drugs and vaccines [2].
The normal physiological functions of GIT are to digest food and to interfere with pathogen entry. These functions need to be considered as peptide drugs and vaccines tend to be digested together with food in the presence of digestive enzymes. The highly acidic pH in the stomach and the presence of proteolytic enzymes such as protease and pepsin can cause protein degradation [1].
Furthermore, they will have difficulties in permeating the physical barrier of the mucus lining, which prevents pathogenic substances from penetrating the cell [3]. Owing to these challenges, protein and peptide drugs are suitable to be administered via parenteral routes such as intravenous or subcutaneous injection [4]. However, these routes require frequent administration with long-term use which will develop patient incompliance to medication [4]. In such a manner, the approach to improve the oral delivery of peptide drugs and vaccines by using suitable polymers are needed to enhance drug effectiveness and patient compliance.
Chitin is the second most abundant polysaccharide present in nature. However, it has more applications when converted to chitosan by partial deacetylation under alkaline conditions [5]. Chitosan is a positively charged polymer that can improve the bioavailability of the oral drug delivery system. It has been used to improve the formulation of peptide drugs, resulting in enhanced cell permeability, which allows an adequate therapeutic concentration of drugs into the systemic circulation [6].
For protein and peptide therapeutics, factors such as poor permeability, luminal, brush border, cytosolic metabolism, and hepatic clearance mechanisms result in their poor bioavailability from oral and non-oral mucosal routes [7]. Oral vaccination is prone to reduce the adequacy of vaccine to be recognised by the immune system due to the presence of gut microbiota and intestinal barrier. Peptide drugs and vaccines can be protected from the degradative barrier of the GIT by encapsulating the drugs into the polymeric chitosan as potential carrier material. The development of nanotechnology, such as nanoparticle systems to transport peptide drugs through the epithelial membrane has been established [6, 8]. Besides, the modification of chitosan is needed to exert its function as a polymer and to protect the drug from enzymatic degradation [9].
This work reviews the physicochemical properties and numerous applications of chitosan, describes its release mechanisms, challenges in oral peptides and vaccines delivery, and strategies to overcome these barriers to improve oral peptides and vaccines bioavailability.
Chitosan is a strong base with linear polysaccharides consisting of D-glucosamine, which contains amino groups [10]. The hydrolysis of chitin will produce chitosan through alkaline hydrolysis or N-deacetylation (Figure 1). Due to protonable amino groups presence in chitosan, this polymer can be easily dissolved in pH below 6.3. However, both chitosan and chitin are insoluble in an aqueous medium.
The N-deacetylation of chitin into chitosan.
Chitin or chitosan is highly available from different species of shrimps, prawns and crabs. These seafood shells release chitosan, which shows properties of antimicrobial and antioxidant activity.
One of the differences between chitosan and chitin is the presence of amino groups. Amino group in chitosan exhibits high solubility in acidic medium and able to form complexes with metal ions. These positive charges interact with drugs and physiological barriers in the GIT, which is useful in the formulation design of the drug delivery system [9].
Some factors affect chitosan properties, including the degree of deacetylation, degree of substitution, and molecular weight [9, 11]. These factors should be considered before using chitosan as a polymer in a drug delivery system. Most of the chitosan applications are affected by these factors through intermolecular or intramolecular hydrogen bonds [12].
The degree of chitosan deacetylation will affect its biological activity, including swelling rate, molecular weight, crystallinity and polydispersity. The deacetylation process leads to the protonation of the amino groups [13]. A highly positive charge will improve the activity of chitosan as mucoadhesive permeation enhancing [14] and haemostatic agent [15]. Sometimes, the degree of deacetylation can be used to estimate the water solubility of chitosan [11] as shown in Table 1.
The degree of deacetylation can influence the particle size and molecular weight of chitosan [13]. The removal of the acetyl group in the structure of chitosan or chitin from deacetylation reduces the interaction between molecules. A low number of acetyl groups minimises the chain length, thus reducing the molecular weight of the polymer [16].
The molecular weight of the polymer will influence the degree of swelling [17]. High molecular weight chitosan (HMWC) tends to have a higher cross-linking ability. Therefore, the drug-coated with HMWC tends to release more slowly [18]. This characteristic is favourable in sustained-release oral drug delivery.
Degree of deacetylation | Level | Water solubility |
---|---|---|
55–70% | Low | Completely insoluble |
70–85% | Middle | Partly dissolved |
85–95% | High | Good solubility |
95–100% | Ultrahigh | Completely soluble |
Relationship between degree of deacetylation of chitosan and their water solubility [11].
Generally, the lower the molecular weight, the higher solubility of chitosan is obtained [13, 19]. HMWC appears in α-chitin crystalline or antiparallel structure. The structure forms after the release of water, which leads to the loss of entropy during aggregation of the polymeric chain [13]. This phenomenon results in the loss of Gibbs free energy. Gibbs free energy (G) is a way to predict the amount of usable energy in the system. Loss of energy means the reaction in the system tends to be spontaneous.
The α-chitin crystalline form exhibit lower water solubility as compared to β-chitin. The shorter polymeric chain of low molecular weight chitosan (LMWC) is unlikely to aggregate [11]. Interaction between molecules declines due to the formation of the hydrogen bonds is limited. A short chitosan chain contains a low number of amino groups [20].
Chitin exists in three different polymorphic forms, which are α-chitin, β-chitin, and γ-chitin (Figure 2). The interaction between C═O⋯NH and C═O⋯OH maintaining the strength of the polymeric network chain [13]. α-chitin appears in its antiparallel structure and the chain is interacting through both inter-and intramolecular hydrogen bond. β-chitin has a parallel structure, which leads to the formation of the intramolecular hydrogen bond. γ-chitin consists of both antiparallel and parallel structure, as it is the combination of α-chitin and β-chitin [21].
The different conformational structure between α-chitin, β-chitin and γ-chitin (adapted from [
β-Chitin exhibits better water solubility but less common as compared to α-chitin [14]. It has been shown that α-chitosan has a higher crystallinity index as compared to β-chitin. However, the crystallinity index for both forms is lower than the raw chitosan [21]. The crystallinity index will increase when the degree of deacetylation of chitosan increases [16].
The β-chitin has a high affinity to the organic solvent due to its structural flexibility [14]. It exhibits higher reactivity than α-chitosan due to a lack of hydrogen bond. This form has a high capability to swell between crystalline structures while losing its crystalline fraction [21]. The swelling of β-chitin sometimes disrupts the polymeric chain and crystalline structure.
The particle size of chitosan plays a major role in developing an efficient carrier for peptide drugs [22]. Monodisperse preparation of nanoparticles is desirable to provide better bioavailability and low toxicity [23]. Polydispersity leads to a larger size distribution, which interferes with the tendency for the nanocarrier to accumulate in the target tissue [23].
Polydispersity describes the degree of non-uniformity of size distribution between molecules due to the aggregation or agglomeration of the polymeric network. It can be estimated using the polydispersity index (PDI), where the ideal index for chitosan nanoparticles is below 0.3 [22, 23]. The degree of deacetylation and molecular weight of chitosan have been proven to influence the polydispersity of the system [24].
PDI increases with an increase in molecular weight. However, it decreases as the degree of deacetylation increases [23]. The increase of amino group protonation and removal of the acetyl group from chitosan structure lead to the enhancement of repulsive forces between molecules and stretch the chitosan to become larger in size [11, 24]. Therefore, the development of chitosan with the optimum degree of deacetylation is needed to minimise the risk of polydispersity. This can be achieved by modifying the time and temperature of the de-
The degree of entanglement for HMWC nanoparticles is higher than LMWC. Therefore, HMWC nanoparticle has a high tendency to aggregate with each other and disrupt the uniformity of the system [25]. However, LMWC cannot be loaded into nanoparticles with smaller size due to its limitation to entangle to the structures of the system [26]. Therefore, maintaining the particle size of the chitosan is crucial in the development of a chitosan nanoparticle.
Modified chitosan shows greater advantages as compared to unmodified chitosan. The modification of chitosan either chemically or physically may improve its solubility, properties of gelling, and biocompatibility. This modification can be done through cross-linking or substitution [27]. The presence of the various reactive functional groups in the chitosan structure makes it available in many derivatives with different stability properties.
A quaternary ammonium salt is a hydrophilic group with a permanent positive charge. Therefore, quaternary chitosan does not need an acidic condition to undergo protonation [12, 28]. It allows chitosan quaternary ammonium salts to be soluble in both acidic and basic pH. This is a good approach to increase chitosan solubility in water [28].
The high strength of the positive charge will weaken the hydrogen bond. However, this activity depends on the degree of substitution. The higher the degree of substitution, the higher the water solubility of chitosan. This will improve the quality of chitosan to act as a mucoadhesive agent that aids the penetration into mucus [29].
Trimethyl chitosan (TMC) is an example of a chitosan derivative from quaternisation. This modification is effective in enhancing the bioavailability of antibacterial drugs with antibacterial properties. Moreover, quaternised chitosan also exhibits antibacterial properties by the interaction of its positive charge with the negative charge of Gram-negative bacteria [28, 29, 30].
Sulfonated chitosan is water-soluble anionic chitosan, which was derived with N-benzyl disulfonated derivative [31]. This modification of chitosan has been shown to be effective, not only as antiviral and antibacterial but also as anticoagulant properties. Sulfonated chitosan interferes with the interaction between the envelope glycoprotein (gp120) and its receptor on the CD4 cells’ surface. Therefore, It inhibits the replication of HIV [32].
Sulfonated chitosan has been developed to carry anticoagulant drugs such as reviparin and enhance the anticoagulant activity. Sulfonated chitosan nanoparticles interact with factor Xa and inhibit their function in the blood clotting mechanism [31, 33]. Low molecular weight sulfoethyl chitosan acts as capping of nanoparticles [33]. A capping agent is needed in the nanoparticulate system to prevent agglomeration.
Amphotericin B is used to treat fungal infection by binding to ergosterol on the cell membrane of fungal. It depolarises the membrane and alters its permeability [34]. Sulfonated chitosan has been used in the formulation of amphotericin B to reduce the side effects of the drug by making sure the drug specifically targets the ergosterol of fungal [35].
The structure of mucin that coats the intestinal epithelial cell contains the cysteine-rich domain. This domain easily forms a disulfide bond with a thiolated derivative of chitosan. The bond formations increase the residence time for the chitosan to the mucus and increase the mucoadhesive property of the chitosan [30, 36]. When chitosan covalently bonded with any thiolated moiety, water-soluble carbodiimide is required as a cross-linker [30]. Carbodiimide increases the number of thiol groups. This enhances the immobilisation phenomena, which is the formation of disulfide bonds due to the activation of carboxylic groups.
The thiolation of TMC with the conjugation of cysteine residue increases the strength of covalent bonding between mucin. The covalent bond formation of chitosan with thioglycolic acid (TGA) is an effective carrier in delivering trimethoprim for urinary tract infection [37]. The preparation of chitosan-TGA nanoparticles should be stabilised by covalent cross-linking with polyanion, such as tripolyphosphate [38]. The cross-linking minimise the risk of particle aggregation, increases the disulfide bond, and strengthens the mechanical force between networks, which allows trimethoprim to be released slowly [37].
The conjugation of chitosan with glutathione will protect peptide drugs from aminopeptidase in the GIT [39]. Glutathione has thiol groups which exhibit strong electron-donating properties. It forms an α-peptide bond with cysteine moiety of aminopeptidase [30]. Glutathione also acts as an antioxidant which reduces oxidative stress and increases the adhesion of formulation to the cell [30].
The poor water solubility of chitosan makes them less effective as a permeation enhancer. The addition of the carboxyalkyl group will transform the molecule into amphoteric in nature and allow them to react in both basic and acidic conditions [40]. The interaction between the carboxyl group and the primary amino group of chitosan exhibits a promising approach in developing controlled drug release.
The Schiff base reactive gives rise to the formation of the N-carboxymethyl derivative of chitosan [41]. This modification of chitosan has been shown to improve the absorption of low molecular weight heparin (LMWH). After coating into polydopamine, the conjugation of LMWH with carboxymethyl chitosan into polyurethane substrate shows excellent hemocompatibility of heparin. This modification enhances the bioavailability and improves the anticoagulant effect of heparin [42].
Propranolol hydrochloride has a short half-life and requires every 6 to 8 hours in a divided daily dose. The use of carboxymethyl chitosan will coat the drug with a polymer matrix. It controls the release of drug with zero-order kinetics, allowing the constant amount of drug will be eliminated per unit time. The hydration of carboxymethyl chitosan will form a gel layered around the drug, which essential in drug release [43, 44].
The release of drugs from the chitosan nanoparticle is influenced by the hydrophilicity of chitosan and pH of the swelling solution. Chitosan release mechanism involves swelling, diffusion of drugs through the polymeric matrix and polymer erosion [45]. Due to the hydrophilicity of chitosan, chitosan nanoparticles exhibit pH-dependent drug and controlled drug release system [6].
Acid and base act as catalysts in the degradation of polymers [46]. Therefore, the behaviour of swelling and the amount of drug released is highly dependent on the pH of the swelling solution. Hence, a modified drug release can be achieved [46]. When polymers get into contact with an aqueous medium, the water will diffuse into the polymer until the polymer swells (Figure 3).
The swelling of swellablepolymers in aqueous medium (adapted from [
The polymeric chitosan chain will start to detangle. The swelling polymer will form pores which allow drugs to diffuse out of the nanoparticulate system [6, 43, 47]. Therefore, the water solubility of chitosan is crucial in the mechanism of drug release from the nanoparticulate system.
Oral drug administration is the most convenient route, especially among the elderly and children. Unfortunately, some drugs and vaccines cannot withstand the physiological barrier of GIT. In the presence of mucus, proteolytic enzymes, and first-pass metabolism by the liver, drugs tend to be degraded or converted into inactive metabolites [48]. Some drugs will be excreted in the urine lead to low bioavailability.
Due to the challenges aforesaid, chitosan and its derivatives have been used in the development of nanotechnology to improve oral drug delivery [25, 30]. It encapsulates drugs to protect them from degradation in the GIT environment. As a consequence of its excellent biodegradable, biocompatibility, and non-toxic properties, chitosan promotes a stimuli-responsive release of drugs. It allows active ingredients to be released from the formulation in a controlled manner, specifically in enteric-coated drugs [38, 43].
Due to its antimicrobial properties, it was used in the delivery of oral antibiotics to eradicate Gram-negative bacteria such as
A peptide is made up of short polymers of ⍺-amino acid, which is around 20 to 50 amino acids. The function of small peptides depends on the functional group of various amino acids. Examples of active peptides are glutathione, bradykinin, angiotensin, vasopressin and oxytocin [4].
Protein is a macromolecular and high molecular weight polypeptide, which is made up of long-chain amino acids (more than 50) arranged in a linear chain through peptide bonds [50]. It can exist in four different structural conformations such as primary, secondary, tertiary, and quaternary. The formation of these structures is dependent on the intermolecular interaction between functional groups of amino acids [51], through covalent bonds or non-covalent bonds.
The covalent bonds are strong bonds which include peptide bonds and disulfide bonds [51]. Peptide bonds are interactions between two consecutive amino acids through amino and carboxyl groups. Meanwhile, disulfide bonds link two cysteine residues through sulphhydryl groups [52].
On the other hand, non-covalent bonds are weak bonds that include hydrogen, electrostatic and hydrophobic bonds. Hydrogen bonds link two different peptides with the hydrogen atom of the N-H group and oxygen of the carboxylic group. Hydrophobic bonds will occur if the hydrophobic nature between non-polar side chains of amino acid interacts with each other [51].
The physiological barriers in the GIT responsible for protecting the body from the entry of pathogens. These barriers may reduce the bioavailability of the protein. The barriers aforesaid include biochemical, cellular, and mucus barriers (Figure 4) [53].
Physiological barriers to oral protein and peptide delivery (adapted from [
The entire GIT has been coated with mucus. Mucus also promotes a physical barrier between the lining of epithelial and lumen [54]. It contains mucin protein which secretes proteolytic enzymes and traps peptide drugs through electrostatic interaction [55].
The epithelium of the GIT consists of an intestinal epithelial stem and microfold cells (M-cell) [48]. These cells are responsible for controlling protein uptake from the gut lumen into the bloodstream. Since protein drug is a macromolecule, the presence of protein complexes between adjacent epithelial cells prevents paracellular transport of drug [56]. Meanwhile, transcellular transport is limited only to highly lipophilic molecules, unless the transportation is mediated by P-gp [57].
Due to the physical and chemical instability of protein in the GIT, they would not achieve an acceptable therapeutic bioavailability. The nature of the GIT as great physiology to digest food will be a barrier for protein drugs to penetrate through the membrane. The challenges and strategies to improve the protein drug delivery through oral administration need to be considered to ensure the drug achieves adequate therapeutic concentration in the body [58].
GIT is the hollow organs include the oral cavity, stomach, small intestine, large intestine, and colon. Each part of the GIT is varying in pH. However, most proteins are stable at neutral pH and tend to undergo protein denaturation at the extreme changes in pH [48]. A building block of protein is sensitive to pH. In the presence of hydrochloric acid in the stomach, hydrolysis will occur and the disulphide bonds of peptide will be reduced.
Acidic pH environment activates the conversion of pepsinogen into pepsin [59], by transferring hydrogen ion (H+). Pepsin is responsible for the breakdown of peptide bonds which will interfere with the structure and stability of the peptide [59].
In the small intestine, the pancreatic juice is secreted in the duodenum. This juice contains pancreatic enzymes and bicarbonate ions (HCO3−) [48]. The pancreatic enzymes consist of amylase, lipase, and protease, which are responsible for the digestion of lipid and peptide. Protease catalyses the proteolysis rate, which cleaves peptide bonds through hydrolysis [4, 58].
The presence of chymotrypsin and peptidase in the jejunum interferes with peptide absorption in the epithelial membrane [48]. Peptide drugs are digested before it reaches the membrane and the fraction of the undigested peptide will reduce. This physiological function will lower the possibility for the therapeutic concentration of peptides to be achieved in the systemic circulation [58].
The layers of the epithelial cell of the intestine are covered by mucus or mucin glycoproteins [55]. These glycoproteins will form a gel layer that covers the surface of the intestinal cell. The diffusion rate for the peptide to the epithelial membrane is restricted in the presence of mucus [54].
One of the intestinal mucosal epithelial cells is the goblet cell. Goblet cells are responsible for secreting mucin 2 in the intestine and Mucin-5b in the colon. Lubricate the passage for chime is the main function of the mucus layer, protecting the epithelium from mechanical damage of GIT [54].
The overexpression of mucin will interfere with the pharmacokinetics of drugs. The higher the concentration of the mucin, the lower the ability of a drug to diffuse through the membrane. Drugs and mucin interact through hydrophobic and Van der Waals interaction.
Large amounts of enzymes present within the mucus layer increase the tendency to digest peptide drugs [58]. The ionic strength, pH, and chyme content in the intestine will affect the charge density in the mucin [54]. The presence of a charged group on mucin interact ionically with charged particles and immobilised them in the mucus. The immobilisation of peptides leads to the clearing from the tract when the layer of mucus is shed [60].
Tight junctions are protein complexes that existed within the adjacent epithelial cells [48]. It prevents leakage and restricts the flux of substances through the paracellular pathway [61]. They consist of transmembrane protein with extracellular domains called Claudin 4 (CLDN4). CLDN4 protects the paracellular physiological function of GIT [62].
The linkage of CLDN4 domains with zonula occludens 1 will result in the connection of cytoskeleton components through linker protein [62]. The components include actin, myosin and microtubules which involve in the contraction of muscle, upon phosphorylation. The contraction leads to cellular tightness, hence, reduce the permeability of substance into the cell.
The effective delivery of oral peptide drugs can be achieved by altering the formulation for maximum solubility, avoid enzymatic degradation and enhance the absorption of drugs through the intestinal epithelial cell [63]. For the sake of preventing enzymatic degradation or inactivation, the addition of enzyme or protease inhibitor is a great approach (Figure 5). Proteolytic enzymes are responsible for cleaving protein molecules into an inactive amino acid chain. Protease inhibitors such as aprotinin and chromostatin can be used to prevent the inactivation of protein drugs [7].
Strategies to improve oral peptide delivery system (adapted from [
As discussed earlier, protein molecules show poor permeability through various mucosal surfaces and biological membranes. The improvement of membrane permeability can be achieved by the inclusion of a permeation enhancer into the formulation. Permeation enhancers are either tight junction selective or membrane perturbing [61].
Chitosan and its derivatives have been used as an enzyme inhibitor, permeation enhancer and mucoadhesive agent [30]. With the different mechanism, modification, and preparation technique, this polymer also involves in the encapsulation of peptide drugs into the nanoparticulate system [60], which protect them from harsh GIT environment.
There are two types of protease, including serine protease and Zn2+-dependent protease. Serine proteases, such as trypsin, chymotrypsin and elastase are pancreatic digestive enzymes. Meanwhile, Zn2+-dependent protease such as matrix metalloproteinase is an insulin-degrading enzyme [64]. Some enzyme inhibitors need chitosan to enhance their anti-protease activity and minimise peptide drug degradation [64]. For example, chymostatin is a protease inhibitor selectively to chymotrypsin-like serine proteases. This inhibitor will covalently be linked to the amino group of chitosan.
The active site of matrix metalloproteinase, such as carboxypeptidase, contains Zn2+ binding motif. It requires Zn2+ to promote nucleophilic attack by water. This protease cleaves membrane-bound pre-proteins of the cell to release cytokine. The ethylenediaminetetraacetic acid (EDTA) is a complexing agent that is capable of forming a complex with Zn2+ and retard the nucleophilic attack of water on carboxypeptidase. To inhibit the Zn2+-dependent protease, the EDTA is covalently bound to the primary amino groups of the chitosan-inhibitor conjugate [27, 65].
Moreover, the study showed that the effect of trypsin inhibitors would be disrupted after the gastric phase. Therefore, the encapsulation of the peptide drug and trypsin inhibitor with chitosan-EDTA conjugates improve the controlled release of the molecules.
Chitosan derivatives improve the permeation of water-soluble drug molecules due to their ability to adhere to the mucus [30]. Thiolated chitosan shows a greater effect in improving drug permeation through the cell membrane. With the formation of disulfide bridges, the thiol group of chitosan interacts with the cysteine-rich subdomains of mucus and allows greater mucoadhesion. Thus, the absorption of the peptide drug molecule increases with residence time [30].
It is worth noting that chitosan with a low degree of acetylation and high molecular weight leads to high charge density. The higher positive charge density of chitosan will bind to negatively charged tight junction channels. Ion displacement occurs, leading to intracellular spaces loosening [16].
The integrity and permeability of tight junctions can be illustrated with transepithelial electrical resistance (TER). The ability of TMC [66] and carboxymethyl chitosan [67] in decreasing the TER will increase the permeability of peptide drugs. TMC has been used to formulate buserelin, a synthetic peptide analogue for LHRH agonist, by the oral delivery system [68].
Thiolated chitosan, such as glutathione, cysteine and N-acetylcysteine, have strong mucoadhesive properties due to covalent bonding with cysteine-rich subdomains of the mucus glycoprotein. For chitosan-glutathione, this derivative improves chitosan stability, enhanced mucoadhesion and permeation enhancing effect. This system has been applied to the oral delivery of immunostimulant drug, thymopentin [30].
Chitosan-cysteine shows similar mucoadhesive but improved cohesion as compared to unmodified chitosan. The cohesiveness of polymeric drug formulation is crucial to ensure the stability of the drug and will be released in a controlled manner. Furthermore, chitosan-N-acetylcysteine produces a longer retention time than unmodified chitosan. However, no drugs have been tested yet for these two chitosan derivatives [30].
By encapsulating peptides into a nanoparticulate system, enzymolysis and peptide aggregation can be avoided. This approach enhances the absorption of peptide drugs through the transmembrane of the small intestinal epithelium [69]. Nanoparticle will provide controlled-release properties in the presence of chitosan as a polymer. This condition will reduce repetitive dose administration and improve drug bioavailability [43]. In the presence of chitosan as a mucoadhesive agent, the retention time between formulation and absorption site will be maximised.
Cyclosporine is a cyclic peptide drug used to suppress the immune system, after organ transplantation. Cyclosporine with high molecular weight (1.32 kDa) shows poor bioavailability with low permeability through the biological barrier. Conventional oral cyclosporine has been shown to have an unpredictable low therapeutic concentration in the bloodstream.
Therefore, a nanoparticle drug delivery system is a promising strategy to improve the oral bioavailability of cyclosporine. Chitosan nanoparticles in the presence of tripolyphosphate, as a cross-linker, make it more convenient as compared to conventional ones. The bioavailability of the nanoparticulate cyclosporine increases by 73% [69]. Exendin-4 is a glucagon-like peptide-1 receptor agonist that has been approved to control type 2 diabetes mellitus. This peptide drug has high susceptible to enzymatic degradation [70]. Chitosan-tripolyphosphate conjugated nanoparticle was used to design oral suspension and enteric-coated capsules of exendin-4 to increase the bioavailability of exendin-4 slightly.
Efflux pump is a membrane protein located within the cytoplasmic membrane of a cell. It translocates a variety of substrates across extra- and intra-cellular membranes. Multidrug efflux pump can be one of the drug resistance mechanisms, as it pumps foreign substances (or drugs) out of cells. This active process is an ATP-dependent [71].
P-glycoprotein (P-gp) is a transmembrane glycoprotein and the best example of a multidrug efflux pump. It is expressed and located in the intestinal epithelium, liver cells and proximal tubule cells of the kidney. P-gp is also located within the blood–brain barrier (BBB), which provides an obstacle for drugs to enter the region. Therefore, it must be difficult for antipsychotic drugs to bypass BBB and exert their effect [57, 71, 72].
Chitosan may enhance drug permeation by opening of tight junctions which is highly related to CLDN4 [73]. Chitosan will modulate CLDN4 protein redistribution to the cytosol and disrupt tight junctions [62]. This phenomenon will enhance paracellular permeability and reduce TER. Thus, declining barrier function of epithelial cells to allow drugs to enter the cell [74].
Furthermore, the use of thiolated chitosan (thiomer) has shown to be useful in bypassing the P-gp. The thiol-moiety of thiolated chitosan may allow the formation of disulfide bonds between the cysteine groups of the P-gp [9]. The thiomers then enter the channels of the P-gp pump together with the therapeutic agent, which obstruct the function of the multidrug efflux pump [57].
For infectious disease by Gram-negative bacteria, chitosan plays an important role in facilitating effective delivery of antimicrobials to the infection site [15, 49]. Chitosan will encapsulate drugs and carry them into bacterial cells by attraction forces between polycationic chitosan and negatively charged bacteria [49]. This action avoids the efflux pump at the cell membrane of the bacterial cell.
Vaccination is one of the most cost-effective approaches to prevent infectious diseases such as hepatitis B, tetanus, polio, and rabies. Vaccines contain pathogens, either live-attenuated, inactive or killed antigen [75]. These pathogens will be administered in the body and recognised by the immune system.
The oral delivery of vaccines is quite challenging as the pathogen is introduced into the body. It is mandatory to ensure mucosal immune response works effectively to protect the body against the pathogen and their toxin [54].
As the vaccine enters the intestine, its presence will trigger the inductive site, the Peyer’s patches. The Peyer’s patches consist of M-cell which will allow the entry of the antigen through endocytosis. The antigen then will be transported into intraepithelial dendritic cells or macrophages and be taken up by the cell through phagocytosis [76].
The antigen-loaded dendritic cell will present the antigen fragment on its surface and triggers the activation of naive CD4+ T-cells. The activated CD4+ T-cells will bind to the antigen fragment, MHC class II. This binding releases chemical mediators, interleukin-2 (IL-2), that function to regulate the activity of lymphocytes for immunity. IL-2 stimulates the cell division of CD4+ T-cells, activates B-cells and cytotoxic T-cells. B-cell is responsible for mediating humoral immunity by differentiating into plasma cells. Plasma cells will generate antibodies to fight against pathogens [77].
Viral protein requires the right structural conformation to attach to the host cell and replicate. Highly acidic in the stomach and extreme temperature changes will cause protein denaturation. The denaturation of the virus will alter the conformation of its structure [58]. The high temperature will break the phosphodiester bond. However, at low temperature, the degradation of the nucleic acid will also lead to viral inactivation [78].
Furthermore, to transport vaccines orally, it should be able to overcome the biological barrier of the intestinal epithelial cell such as tight junction and mucus. The hydrophilic antigen cannot cross the phospholipid bilayer to enter systemic circulation due to the function of tight junction in controlling the permeability of the membranes. Therefore, the uptake of the antigen to mucosal tissue is limited with a short time of exposure [78].
The GIT contains normal flora or microbiota which help in maintaining the structure of the gut mucosal barrier [55]. Those microbiotas not only aid nutrient metabolism, but they also possess an action to protect against invading pathogens [79, 80]. Well-balance microbiota is needed to induce the effectiveness of vaccines through oral administration. The delivery of the vaccine will be interrupted in patients with microbiota dysbiosis, leading to blunted vaccine response [80].
The induction of danger signals appropriately by the vaccine is essential to trigger an immune response [81]. Due to these limitations, there is a problem in inducing an adequate immune response against administered pathogens [3]. Consequently, a higher and repetitive dose is required. Nevertheless, the administration of high antigen doses repetitively may develop systemic oral tolerance towards vaccines [3, 78].
The uptake of antigen by immune cells depends on the particle size of the antigen. The smaller size of pathogens is readily taken up by dendritic cells [75]. The same goes for peptide, encapsulation of pathogens in nanoparticles is a good approach to improve the effectiveness of vaccines in stimulating the immune system [75].
Small particle size is required to penetrate the mucus. The formulation will be excluded out from the layer of mucus if particle size greater than normal mucus pore size (100–500 nm). This leads to the interruption in the bioavailability of antigen to targeted antigen-presenting cell (APC). Therefore, the development of nanoparticulate systems is required to provide a smaller size (20 – 40 nm) of formulation [82].
Medium molecular weight chitosan (MMWC) with the degree of deacetylation of 85% has been shown to improve the delivery of ovalbumin antigen with the presence of alginate and calcium phosphate (CaP). CaP has adjuvant properties by activating the surface expression of B-cell. CaP can be coated with mucosal penetrating polymers, such as chitosan and alginate to avoid biodegradation by enzymes present in the GIT [82]. In the stomach, the alginate-chitosan-coated CaP nanoparticle delays the release of ovalbumin antigen. The antigen then will be released in the intestine and colon with a sustained-release mechanism. This nanocarrier has successfully encapsulated ovalbumin antigen with small size (< 50 nm) [82].
The antigen should be transported to the intestine and directly to the M-cell of the Peyer’s patches [6]. Chitosan develops well-protected mucoadhesion by prolonging the residence time at mucosal surfaces. The uptake of antigen by epithelial cells of the intestine will be improved by chitosan. An increase in the activity of macrophages will improve the secretion of mucosal IgA and IgG [76].
Chitosan-based drug formulation has gained attention for their ability to serve as a carrier and an enhancer for oral delivery of peptides and vaccines. Although oral delivery is the most convenient and preferred route of administration, however, it has limitations due to the presence of the proteolytic enzyme, pH of GIT and the intestinal barrier to drug absorption. In recent years, there has been considerable research interest in the application of chitosan as an enzyme inhibitor, mucoadhesive agent and efflux pump inhibitor. Interaction of positively-charged amino groups of chitosan with negatively-charged sialic acid groups that exist in mucin prolongs the residence time between drugs and membranes, therefore enhancing the bioavailability of the drugs. Other formulation strategies include encapsulation of proteins, peptides and vaccines into a nanoparticulate delivery system. By encapsulating peptide into a nanocarrier system, the enzymolysis and peptides aggregation can be avoided thus enhances the absorption of peptide drugs in the intestinal epithelium. Similarly, encapsulation of pathogens in nanoparticles is a good approach to improve the effectiveness of vaccines in stimulating the immune system.
The authors acknowledge Faculty of Pharmacy, Universiti Teknologi MARA and internal grant (DUCS) 2.0, 600-UiTMSEL (PI. 5/4) (016/2020).
The authors declare no conflict of interest.
Kilodalton Nano-metre Gastrointestinal tract Gibbs free energy Polydispersity index Low molecular weight chitosan High molecular weight chitosan Medium molecular weight chitosan Trimethyl chitosan Transcellular electrical resistance Thioglycolic acid Low molecular weight heparin P-glycoprotein Claudin 4 Ethylenediaminetetraacetic acid Interleukin-2 Antigen-presenting cell Calcium phosphate Polyethylene glycol Pegylated chitosan Hydroxypropyl methylcellulose phthalate
There are 155 universities in Thailand, which are governed by the Ministry of Higher Education, Sciences, Research and Innovation (MHESRI). The universities are categorized according to the structural and administrative systems into 3 groups, namely, 26 autonomous universities, 57 governmental universities, and 72 private universities [1]. Additionally, certain other higher education institutions offer their programs in specialized fields. These institutions are affiliated with governmental organizations such as the Ministry of Public Health, the Ministry of Defense, and the Ministry of Interior. Almost all universities in Thailand run a closed instructional system, while only two universities offer an open or distance system.
The presently emerged disruptive technology has brought great impact on the management of higher education in Thailand. It is caused by several environmental changes both internally and externally: (1) The total change of employment in the government and the private sectors due to the need for digital transformation leads to decreasing job positions and employment rates. Required knowledge as well as skills of applicants to the jobs changed. Meanwhile, universities so far have not been able to prepare manpower who possess the competency required by the job markets. (2) Under the digital university policy, universities receive impact from disruptive technology, and adjustments become a must by applying technologies in the administration, operation, service, and instruction. (3) The attitudes toward higher education have changed because recruitment of people in the industrial sector no longer emphasizes degree certificates, but working competency. In addition, the population aged 18–22 years or the Gen z have unlimited channels to acquire knowledge and develop themselves in the digital world, and have more chances to build incomes from online businesses or from independent jobs without having to rely on mainline higher education programs [2].
Besides the need for adjustments to face disruptive technology, Thai higher education institutions are also confronted with threats related to reputation building and work outcomes at the international level. The 2020 report of the Office of National Higher Education Science Research and Innovation Policy Council stated that IMD World Competitive Rankings 2020 placed Thai universities at the 49th order from 64 countries, in terms of educational qualities [3]. It can be seen that the ranking of Thailand is among the low group when compared to other countries in Asia, especially when the quality is related to economic competition. This means that Thai universities fail to prepare graduates with the requisite qualifications of the industrial sector. The expected traits of personnel by the job market include skills in creating innovation besides academic knowledge and competence. This fact corresponds to a report by the World Economic Forum, in which the most essential 10 skills for 2025 employment are as follows: (1) analytical thinking and innovation, (2) active learning and learning strategies, (3) complex problem solving, (4) critical thinking and analysis, (5) creativity, originality and initiative, (6) leadership and social influence, (7) technology use, monitoring and control, (8) technology design and programming, (9) resilience, stress tolerance and flexibility, and (10) reasoning, problem-solving, and ideation [4].
The impact of disruptive technology results in a lot of transformation of education and instructional operations in Thai universities. Many universities have turned to rely on education transformation strategies in order to expedite the changes. Khon Kaen University, for instance, sets the strategic educational transformation by enhancing outcome-based curricula instead of the former content-based curricula, and by changing from teaching to learning in the instruction system [5]. At the national level, the MHESRI has come up with the new species of graduates project to respond to the needs for manpower in the industrial sector. This is also an important mechanism for the national economic propulsion, which has been put into action through the transformation of instructional and curricular methods and from the collaboration between the higher-education institutions and the industrial sector, government, the civil society, or community toward the university education for the future. The said sectors joined in prototype program design that emphasizes the transformation of content, elements, and curricular structure. The collaboration also involves instructional management that essentially builds learning experiences through working in the “real situation” [6].
It can be said that before the spread of Covid, Thai higher education already altered the system to the smart education, which means the system that targets preparation of manpower with knowledge and abilities to lead their lives and work that responds to the needs of the present digital market [7]. Glasco [8], in addition, explained that smart education is the genre of education for the new generations of digital natives. Compared to the former instructional methods, smart education emphasizes interaction, collaboration, and engagement between the teacher and learners and between learners and learners so that sustainable and continuous learning skills will be acquired by the learners. Moreover, outcome-based education has been introduced, in which the learning competency development in learners is the keyword. The instruction emphasizes learning from practices rather than from theories or learning from doing activities to obtain real experiences and from doing the job (work-integrated learning) [9, 10].
McLellan [11] explained that the high-capability Internet technology allows people from every corner of the world to communicate and work together efficiently. Thus, the production sector needs people who are able to use technologies to contact customers or colleagues that are from multiple backgrounds and culture. Manpower building does not, therefore, target only the learning outcomes in terms of knowledge and advanced thinking, but also, the process has to set the competency that incorporates multi-dimensional capabilities. What has been said agrees with the OECD Learning Framework 2030, in which the concept for essential competencies for the future is mentioned. The word competency is not only composed of knowledge and skills, but it also integrates bodies of knowledge, skills, attitudes and values that enable one to move on until one achieves his mission [12].
For the instruction that is based on competency development, the teacher, besides having to answer the important question, “What are the necessary knowledge, skills, attitudes, and values for learners and entrepreneurs?”, must be able to answer the question, “How can instruction be designed that will effectively develop knowledge, skills, attitudes, and values of the learners?” [13]. In this respect, the instructional design that develops learner’s competency and the said qualities necessitates multiple sorts of activities, which, more importantly, learners should be learning in a real situation. The knowledge content must be accurate and up-to-date, and can be applied in real contexts. Development of skills should be performed in the situation similar to the real workplace, not confined within a laboratory or a simulated venue. It is certain that incubation for good attitudes and values toward what learners do or act depends on the social context of real working condition. Therefore, many Thai universities have been enhancing and provoking outcome-based curriculum and encouraging teachers to apply competency-developing techniques such as problem-based learning (PBL), task-based learning, experience-based learning, and work-integrated learning. These methods had not caused any problem during the time before the Covid pandemic, since in general, they were conducted in classrooms and through a practicum at workplaces.
When the coronavirus (COVID-19) began to spread in Thailand at the beginning of January 2020, most Thai universities were entering the second semester of the academic year. The MHESRI [14] announced that all universities had to carry out instruction online only. However, during that time, each university had not prepared any facilities for online teaching. It became the responsibility of lecturers to acquire tools, equipment, and technologies for their teaching, not to mention that they had to learn how to use the technology on their own. The most controversial issue was online examination administration. Since the time was approaching the end of the semester, many courses stopped class meetings and were at the stage of learning evaluation. Normally, all universities schedule the final exam week, which is based on on-site administration, where identification of students taking the examination is strict according to the university’s regulations. Online examination, on the contrary, has certain constraints. The interesting phenomenon thus emerged; that is, most lecturers had to change their student assessment and evaluation method, by relying on various authentic assessment approaches that measure the students’ learning achievement. Tools have been developed for measuring the learning outcomes under the authentic assessment method according to the Thai Qualification Framework for Higher Education (TQF) [15].
Most of the learning assessment and evaluation tools are the evaluation platforms modified from the surveying technology, for example, Google Form [https://docs.google.com/forms/u/0/?tgif=d] or Microsoft Form [https://www. office.com/launch/forms?auth=1]. Some rely on the testing system, which is an integrating function in the learning management system (LMS) such as Moodle LMS. These tools can only assess the learning achievement in terms of knowledge content. They still have limitations in assessing learners’ skills, which require observation or following up of students’ practices. Moreover, there is no regulating or administering system for the examination that prevents copying or cheating in an examination. Universities, therefore, find it necessary to develop a technology or tool for the administration of examinations that does away with cheating and results in efficient examination and assessment.
Since the COVID-19 pandemic is still ongoing, and together with threats from the disruptive technology, universities have to change and become prepared for organizing online instruction. Analyses of data from the Web sites and media of different universities showed that the implementation related to the transformation from an on-site to the online system involves many aspects: (1) Improvement of technological infrastructures that support online teaching and learning; (2) Procurement and development of platforms for online teaching and learning; (3) Teacher training so that they are able to use the technology and tools, and are able to organize online teaching and learning (including design of learning management, development of learning media, management of online classrooms, arranging learning activities, and assessment of learning outcomes). As far as the students are concerned, most universities had to prepare their students for the online system that they join from home. As a result, some universities such as Khon Kaen University offer a computer-lending system, with a sim card for the internet use that allows them to have access to different learning sources. The training was organized for all students to be able to use the learning technology and tools as well as research and production of learning outcomes in different forms. It can be said that the COVID-19 pandemic and the building of online learning platforms for the learners [16] are the stimulants for total education transformation in all universities from classroom instruction to online instruction.
Somabut [17] conducted a survey on the condition of and students’ opinions towards online instruction at Khon Kaen University in 2020, during the spread of COVID-19. The sample group that answered the questionnaire administered online comprised 1,339 students and 253 lecturers. The following information was found: The equipment and technologies mostly used by the students were: Windows laptops (46.45%), smartphone operating system (iOS) (43.76%), and android operating system (40.33%). The most wanted media and learning activities included lecture videos (74.91%), live lectures via video conference (66.77), and discussion forums with teachers (49.51%). In terms of lecturers, it was found that most relied on lecturing by means of video conference (87.65%), followed by assigning students to study for additional content and draw the conclusion from it (76.34%), and video-recording the lecture, assigning students to pre-study the topic and present their work or discuss by means of video conference (45.32%). Most of the media used by lecturers were slides that conclude the content to accompany the lecture (93.25%), handouts produced by the lecturers (76.5%), and retrieved documents from various sources (67.43%). The technology for instruction included video conference (85.34%), social media (71.55%), and LMS as the learning management systems (67.48%).
It can be said that most of the online instruction does not differ from the former approach, for most lecturers still lecture. The popular platforms are: Zoom, Meet, Microsoft Teams, and WebEx. The learning management systems (LMS) that are mostly relied on are Moodle LMS (which is installed in the server of many universities), Google classroom, Microsoft teams, which are used by most lecturers to make announcements for the course, assign learning projects, and for students to submit their learning missions. Most of the media were slides that accompany lectures and videos describing the content so that students can prepare before class or listen to it after class. Textbooks or sheets have been made as digital documents for ease of uploading to the LMS for the learners. The tools for learning assessment have just been developed. Many universities have procured platforms made in the market and subscribe to these per year or many years. The lecturers can thus use these platforms. Some universities (few) have developed their learning assessment method, including data management for examination and preventive systems against rule-violating actions or cheating. Khon Kaen University has developed an examination administering system along with the learning management system, called: KKU Exam [https://exam.kku.ac.th/]. This has been installed in the university’s Moodle LMS and has a capacity of at least 8000 people per test.
For the instruction that is principally based on online systems, drawbacks in practices are unavoidable. For instance, distance communication has a limitation in expressing emotion, feeling, and empathy, especially when problems are consulted, explanations that required empathetic and close talks, changing the mindset of learners to stimulate interest and participation. These can be a complicated task of online channels [18]. However, with the capabilities of technologies, opportunities can be gained from online instruction such as rapid communication, multiplicity, and vastness of information, reduction of travel, and time for learning. These opportunities can be used in managing the learning ecology for efficient online education [19].
The higher education paradigm has been changed for some time, especially the concept in curricular design and instruction, which was formerly based on knowledge and understanding of contents more than applying the knowledge in the work or working skills that are separated from knowledge and context of the workplace, towards the design of curriculum that emphasizes competency. The first question formerly asked when designing a course was, “What are the contents to be taught?”, whereas now, the question is, “What competency should be incorporated in the course instruction?” Answering the new question is challenging, as it involves also the competency required by a workplace or the job market. It is the same question for which the lecturer must analyze and classify into at least 3 sub-questions that clarify what is needed for learners to acquire the said competency: (1) What knowledge is necessary? (2) What skills are necessary? Or what should the learner be able to do? (3) What are the required traits learners should have? Nevertheless, whatever is the instruction system, online or onsite, the competency objective must be met [12].
Although the paradigm in curricular design and instruction has changed, the design and promotion of learning still are principally based on the constructivist theory. This theory explains that learning or knowledge is built by an individual from perception of new information or data, which is then interpreted using the former schema or experience as the base in order to construct the new meaning. Constructivists believe that even though people receive the same information from various channels, interpretation or construction of new knowledge may differ, and for former knowledge, experience of each is different [20, 21]. In short, the learning concept of constructivist is the fact that knowledge and learning is an individual’s matter; thus, learning and knowledge construction arise from that individual. Learning in constructivist’s perspective is believed to be enhanced and stimulated from the inner process of the learner and the surrounding society that helps the learning process to be complete [21, 22]. Therefore, instruction based on constructivist can be used as the basis for developing knowledge, skills, attitudes, and values of the learner. It emphasizes learning by learner’s action or acquisition from experiences in the real context.
During the spread of COVID-19, students have to learn from their dormitory, home, or apartment. They cannot learn in classrooms or on campus as usual. Online learning is a new experience for students. Most have never been exposed to 100% online learning. Some problems may arise among learners such as responsibility, self-regulations, planning of their studies, self-assessment of their learning, and time allocation for their learning mission. Nevertheless, most students are digital natives; therefore, they do not have a problem with the use of technology and learning tools. Besides, university students are the Gen z, who already possess the following behaviors: learning by doing and learning from seeing and listening. Because they grow in parallel to YouTube and moving learning media, they enjoy communications via social media and are able to communicate or work with others whom they do not know by using different technologies [23]. Therefore, online instruction management should take into account the learning behaviors of the learners as the important element.
From the discussed learning management and learning behaviors, curricular design and online instructional management at the higher education level should be based on the following online teaching and learning ecology (OTLE) (Figure 1).
Online teaching and learning ecology (OTLE).
In order to be in line with the development of learners’ competency, where knowledge, skills, and required traits must be developed, the methods and learning activities must correspond to each competency enhancement. The instructional management approaches may be as follows:
Raising doubts of students from giving a problematic situation, a real event, or a problematic context that students have encountered. The story used for raising doubts should be complex and necessitates advanced thinking to solve the problem. More importantly, it must be in a real situation [24].
Presenting and informing the goal and learning approaches to students, opening up the chance for students to voice their opinions, negotiate, and set the target and learning activities together.
The design of learning activities and assessment must be associated with the stimulation and enhancement of knowledge construction, development of skills, and required traits of learners.
Arranging learning activities that emphasize the roles, learning actions, and self-regulation of learners. It needs to be emphasized that knowledge and skill construction is not a reproduction of content or knowledge [25].
The learning activities, besides developing knowledge and skills according to the learning objectives, must develop problem-solving skills and advanced thinking as well as profound understanding [26].
The learning assessment and evaluation should be designed and made in accordance with the framework of competency, that is, assessing the knowledge, skills, and traits [27, 28].
Classroom management in the new era, especially during the disease pandemic has resorted to the so-called virtual classroom, which in fact has been developed for some time. Now, it has to be used concretely, that is, in the form of an online virtual classroom. From an online virtual classroom, various functions must be usable as they are in on-site classes. For instance, the teacher and students must be able to carry out learning activities, and the followings must be doable: assignment, grading, exchanging of opinions, presentation, preparation of media, content, or information useful for learning. The content and learning resources should be in agreement with the behaviors, requirements, or the learning context of the present-day learners. Followings are suggestions for technologies and learning resources preparation [29, 30, 31].
The technology that promotes and facilitates learning should at least include the following modules: managing user’s account, assignment, grading and comment, presentation of content and resource, discussion and exchange of opinion (forum), announcement related to instruction, assessment tool and collaboration tools.
The platforms used for learning management must facilitate learners and teachers, and enable them to discuss, share experiences, and work together smoothly with no complication.
Information source and content should provide both the primary source and the content summarized by the teacher.
The content for the students should be in multiple forms, such as video, text audio graphic, or animation, depending on the nature and characteristics of the content, so as to meet the interest and learning behaviors of learners that can vary.
Apart from content and learning sources, the teacher may have to select the problem cases that are close to the content in the lesson so as to facilitate learners whose experience in the content may still be little.
If it is necessary to produce a video clip for lecturing the content, each clip should not be longer than 20 minutes. If the content is wide, it should be divided into sub-topics.
In the new era of classroom management, what teachers should learn and train to use to the expertise level is digital technology application for teaching, which may not be just online lecturing. Teachers need to learn to use LMS that will be developed into a virtual classroom, technology for assigning work, grading and comment, assessment and evaluation based on digital technology. Besides, teachers must take more roles in planning the learning, presenting the plan to learners so that they can make their own plans and adjust the learning with the teacher. Learning plans may involve many approaches. The teacher has to accept each student’s context. The roles of teachers at the higher education level in online instruction management should be as follows: [32, 33]
Design and plan learning by analyzing the learning competency goals, learning activities, assessment, and media or learning content.
Change the role from content expert to a guide, monitor, coach, tutor, and facilitator. These roles will be acted through the medium of digital technology.
Survey and search for new instruction management that corresponds to the learner’s learning style, especially the strategy that stimulates students to learn freely according to the goal.
Use the mistakes or misunderstandings of the students as the opportunity to change their knowledge concept. They may need advice for revising their former understanding.
Give positive feedback to the students. This is an important strategy to enhance individual learning for the new age learners, who want to know which points they need to adjust and by what means. Feedback on a person-to-person basis is essential despite its time consuming.
Besides being an expert, a coach, or a monitor, the teacher may change the role and becomes a learner who learns with the students so that the teacher is able to see from the students’ multiple perspectives while at the same time, not feeling too distant away.
The upskilling of the use of digital technology in instructional management is unavoidable and cannot be refused. From the present stage, learning that relies on technology will be more accepted. Re-skills in terms of teaching and learning tactics are necessary in order to be in line with learners’ changing of context and behaviors. Teachers should not be trapped within the complaints of the students’ changes, but have to adjust their methods to accommodate those changes instead.
Superficially, learning through online platforms seems to offer freedom. Learners can design their learning and do their own learning activities. They are able to set the activity, time, and place by themselves. Formerly, learning was confined according to what had been planned by the teacher, or students learned from the assignment given by the teacher of each course. This resulted in tension, for students had to hand in the assignment within the limited time frame. Students might not be able to plan their learning with the teacher, but just followed what the teacher planned and assigned. In the new learning era, most roles must be played by the students, from the beginning until the conclusion, so that the outcomes will stay with the students. The teacher only designed the course at the beginning, and prepared learning aids and content as seen necessary. Learning activities, knowledge construction and skill training, will be within the scope of the students’ role. Therefore, learning management may involve the students’ roles as follows [34, 35, 36]:
Set the goal and plan the learning and assessment activities with the teacher, by taking into account one’s own context that will lead to the achievement of the learning objectives.
Besides planning the learning with the whole class, each student must plan individual’s learning of each subject, which may differ from others. The plan will lead to self-control and self-monitoring to achieve the goal.
The skills and personal traits to be used by each student in order to achieve the learning goal should comprise metacognition, self-analysis, self-regulation, self-reflection, and self-awareness.
Digital competency must be developed and is each student’s responsibility, both including hard skills and soft skills, as the important tools that enable efficient digital learning. Learning is via digital platforms, and thus the learners need the tools for communicating, developing and creating work outcomes, searching, compiling, and managing media and information sources, as well as knowing the rules and courtesy to be used in the digital world, knowledge related to patents and rights to use the media and content in the digital world.
The construction of knowledge and skills of the learner requires analysis, interpretation, and decision making by using the former knowledge and experiences. New information may improve the former beliefs, knowledge, and attitudes.
Utilize the opportunity in having the learning freedom and the capacity of digital technology by setting the learning target. Students may have to question themselves what they want to know, what they want to be able to do, what for, and what learning tools are necessary.
In order for learning to be complete, the constructed concept, knowledge, and understanding may have to be presented to others such as the teacher or friends in the class. This is to confirm the understanding, or for exchanging viewpoints. However, after discussion, students do not have to change their understanding if the reason can be more clearly explained than others’ comments.
The management of instruction in the new era is under the constraint of area and place. Digital technology is an important factor that brings efficiency in learning management. The preparation and improvement of the technological system may be beyond the responsibility of university lecturers. Thus, university administrators or the department involving with system development and technological infrastructures must revise and plan the digital technology strategies in order to cope with the use by both lecturers and students. These are the successful conditions of virtual university. Followings are the issues to be implemented:
Evaluate the status and readiness of the system and digital technology, modernize it, make it highly potential and respond to teaching and learning management and urgent use.
Adjust the tool and technological platforms that are categorized as low-code tools to reduce the time to develop new tools and systems, since they are already familiar to people in the organization.
Support in terms of necessary materials and equipment for online learning, both for the teachers and students.
Develop several forms and frameworks for efficient learning management that enable teachers to choose according to the context of each course.
Train both staff and teachers, and teaching supporters who have to work with the digital technology and distance working, of which most may not be familiar with.
Closely monitor and evaluate the teaching in order to use the results in adjusting the policy and implementation in time. This does not have to be a long-term or a 1-year policy, but can be done each semester.
Prepare the students for online learning by building an understanding of the roles, duties, and practices, including training how to use digital tools for learning.
Under the pandemic of COVID-19, universities in Thailand are attempting to adjust themselves to pass the crisis. The action done is to change the channels in teaching to be online so that bodies of knowledge can be transferred and communications made possible with students. Although the implementation may not be very good, learning and adjustments of learning methods are being attempted to pass through the crises. If considering sustainability, the learning methods may be changed, while the target of competency development remains. Instructional management method that aims toward sustainability should rely on technology for the development of virtual classroom or virtual university. This is similar to the online world that permits teachers and students to perform learning activities, meet, and discuss, with facilities supporting the activities and the work [37]. Such technology is only a facilitating tool, but the heart of learning is the design of learning activities in virtual classroom that corresponds to the goal of the curriculum, learners’ learning style, and context. The design of learning activities must also be in accordance with the functions of modern tools and technology. Besides, those directly involved in teaching and learning, that is, teachers and students, must accept the virtual classroom condition in terms of impossible items. There are many things that are the opportunity in virtual instruction, for example, freedom to plan the learning, searching and rapidly accessing the multiple sources of information, and quick and convenient communication. Thus, besides the skill in the use of digital tools for teaching and learning, both the teachers and students must adjust their mindset in perceiving online learning.
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However, agricultural malpractices like excessive use of chemical fertilizers and pesticides, as well as climate change have aggravated the effects of biotic and abiotic stresses on crop productivity. These led to the degradation of ecosystem, leaving bad impacts on the soil qualities and water body environment. As an alternative to the rising agricultural energy, the use of Vesicular– Arbuscular Mycorrhizae (AM) may be a better option. Being natural root symbionts, AM provide essential inorganic nutrients to host plants, thereby improving its growth and yield even under stressed conditions. AM fungi can also potentially strengthen the adaptability of a plant to the changing environment, as a bio-fertilizer. The chapter provides a comprehensive up-to-date knowledge on AM fungi as a tool for sustainable agricultural system. 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Lentil crops are vulnerable to a number of diseases caused by fungi, viruses, nematodes, insect pests, parasitic plants and abiotic stresses. Among them, the most significant and serious soil-borne disease is Fusarium wilt (Fusarium oxysporum f.sp. lentis: Fol). Fusarium wilt causes yield loss up to 50% in farmers’ fields. The pathogen showed high levels of phenotypic and genotypic diversity in India, Algeria, Syria and Iran. The disease thrives at 22–25°C temperature and affect lentil either at seedling and vegetative or the reproductive stages of the crop. To minimize yield losses, an integrated management strategy comprising resistant/partial resistant cultivars, adjusting sowing time, bio-control and chemical seed treatments is the best approach to reduce the incidence of the Fusarium wilt of lentil. 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