Table Of Content

Woodhead Publishing Series in Biomaterials EMERGING APPLICATIONS OF CARBON NANOTUBES IN DRUG AND GENE DELIVERY Edited by PRASHANT KESHARWANI Assistant Professor, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India WoodheadPublishingisanimprintofElsevier 50HampshireStreet,5thFloor, Cambridge,MA02139,UnitedStates TheBoulevard,Langford Lane,Kidlington,OX5 1GB,UnitedKingdom Copyright©2023ElsevierLtd.Allrightsreserved. Nopart ofthispublicationmay bereproduced ortransmittedinanyform orbyany means, electronicormechanical, including photocopying,recording,orany information storageandretrieval system,without permissioninwritingfrom the publisher.Details onhowtoseekpermission, furtherinformation aboutthe Publisher’spermissions policies andourarrangementswithorganizations suchasthe CopyrightClearanceCenterandtheCopyrightLicensingAgency,canbefoundatour website:www.elsevier.com/permissions. Thisbookandtheindividual contributionscontainedinitareprotected under copyrightbythePublisher (otherthanasmaybenotedherein). Notices Knowledgeandbestpracticeinthisfieldareconstantlychanging. Asnew research andexperiencebroadenourunderstanding, changesinresearch methods,professional practices,ormedical treatment maybecomenecessary. Practitionersandresearchersmustalwaysrelyontheir ownexperience andknowledge inevaluating andusingany information,methods,compounds,orexperiments describedherein. Inusingsuchinformation ormethods theyshouldbemindfulof theirown safetyandthesafetyofothers,includingpartiesforwhomthey havea professionalresponsibility. Tothefullestextentofthelaw,neither thePublishernortheauthors,contributors, or editors,assume anyliabilityforanyinjury and/ordamagetopersonsorproperty asa matterofproductsliability,negligence orotherwise,or fromanyuseor operationof anymethods,products, instructions,or ideascontainedinthematerialherein. ISBN:978-0-323-85199-2 Forinformation onallWoodhead Publishingpublications visitour website athttps://www.elsevier.com/books-and-journals Publisher:Matthew Deans Acquisitions Editor: SabrinaWebber EditorialProjectManager:JoshuaMearns ProductionProjectManager:Prem KumarKaliamoorthi CoverDesigner: Mark Rogers TypesetbyTNQTechnologies Contributors Mohammad A.S.Abourehab Department ofPharmaceutics, CollegeofPharmacy, UmmAl-QuraUniversity,Makkah, SaudiArabia;Department ofPharmaceutics andIndustrial Pharmacy,College of Pharmacy, MiniaUniversity,Minia,Egypt Mustafa A.Alheety Department ofNursing, Al-HadiUniversity College,Baghdad,Iraq Duygu Beduk Department ofBiotechnology, GraduateSchool ofNaturaland AppliedSciences,Ege University,Bornova, Izmir,Turkey Sanghamitra Chatterjee Department ofChemistry,Instituteof ChemicalTechnology, Matunga, Mumbai, Maharashtra, India Pavan KumarChintamaneni Department ofPharmaceutics, GITAMSchoolofPharmacy, GITAM-Hyderabad Campus, Hyderabad,Telangana, India RambabuDandela Department ofIndustrialand EngineeringChemistry, InstituteofChemicalTechnology Mumbai-Indian OilOdishaCampus, Bhubaneswar,Odisha, India MahdiehDarroudi Department ofPhysiology, Facultyof Medicine,MashhadUniversity ofMedicalScience, Mashhad, Iran Ceren Durmus Department ofBiotechnology, GraduateSchool ofNaturaland AppliedSciences,Ege University,Bornova, Izmir,Turkey Lopamudra Giri Department ofIndustrialand EngineeringChemistry, InstituteofChemicalTechnology Mumbai-Indian OilOdishaCampus, Bhubaneswar,Odisha, India IsraelGonzález-Méndez InstitutodeInvestigaciones enMateriales, UniversidadNacional Autónoma deMéxico, Circuito Exterior CiudadUniversitaria, MéxicoCity,Mexico Kenguva Gowtham Department ofIndustrialand EngineeringChemistry, InstituteofChemicalTechnology Mumbai-Indian OilOdishaCampus, Bhubaneswar,Odisha, India SimgeBalaban Hanoglu Department ofBiotechnology, GraduateSchool ofNaturaland AppliedSciences,Ege University,Bornova, Izmir,Turkey ix x Contributors DuyguHarmanci CentralResearch TestandAnalysisLaboratory Applicationand ResearchCenter, Ege University,Bornova,Izmir,Turkey Gowtham Kenguva Department ofIndustrialandEngineering Chemistry,Instituteof ChemicalTechnology Mumbai-IndianOilOdishaCampus, Bhubaneswar,Odisha,India PrashantKesharwani Department ofPharmaceutics,School ofPharmaceutical EducationandResearch,Jamia Hamdard,NewDelhi,Delhi, India;UniversityInstitute ofPharmaSciences,Chandigarh University,Mohali,Punjab, India RenatR.Khaydrov InstituteofNuclear Physics, UzbekistanAcademyof Sciences,Tashkent, Uzbekistan MajidKhazaei Department ofPhysiology, FacultyofMedicine, MashhadUniversity ofMedicalScience, Mashhad, Iran;Metabolic Syndrome Research Centre,MashhadUniversity ofMedical Science,Mashhad, Iran PraveenT.Krishnamurthy Department ofPharmacology, JSSCollege ofPharmacy (JSSAcademy ofHigher Education&Research),Ooty, TamilNadu,India G.Kusuma Kumari Department ofPharmacology, JSSCollege ofPharmacy (JSSAcademy ofHigher Education&Research),Ooty, TamilNadu,India Javier Lara-Romero FacultaddeIngeniería Química,UniversidadMichoacana deSan NicolásdeHidalgo, Morelia,Michoacán,México AhmedR.Mahmood Department ofMedicalLaboratory Technology, ImamJa’afarAl-SadiqUniversity, Kirkuk,Iraq Abdulwahhab H.Majeed Department ofChemistry,Collegeof Science,DiyalaUniversity,Diyala,Iraq LeqaaA.Mohammed Department ofChemistry,Collegeof Science,DiyalaUniversity,Diyala,Iraq SeyedehElnazNazari Department ofPhysiology, FacultyofMedicine, MashhadUniversity ofMedicalScience, Mashhad, Iran AmmuV.V.V.Ravi Kiran Department ofPharmacology, JSSCollege ofPharmacy (JSSAcademy ofHigher Education&Research),Ooty, TamilNadu,India MajidRezayi MedicalToxicology Research Centre,MashhadUniversity ofMedicalScience,Mashhad, Iran;MetabolicSyndrome Research Centre,Mashhad UniversityofMedical Science, Contributors xi Mashhad, Iran;Departmentof MedicalBiotechnology andNanotechnology, Schoolof Science,MashhadUniversity ofMedical Science,Mashhad, Iran Ernesto Rivera InstitutodeInvestigaciones enMateriales, UniversidadNacional Autónoma deMéxico, Circuito Exterior CiudadUniversitaria, MéxicoCity,México Smruti RekhaRout Department ofIndustrialand EngineeringChemistry, InstituteofChemicalTechnology Mumbai-Indian OilOdishaCampus, Bhubaneswar,Odisha, India AndreaRuiu InstitutodeInvestigaciones enMateriales, UniversidadNacional Autónoma deMéxico, Circuito Exterior CiudadUniversitaria, MéxicoCity,México Amirhossein Sahebkar AppliedBiomedical ResearchCenter, MashhadUniversityof MedicalScience,Mashhad, Iran;Biotechnology ResearchCenter, Pharmaceutical Technology Institute, Mashhad University ofMedicalSciences, Mashhad,Iran;Department ofBiotechnology, School of Pharmacy, MashhadUniversityof MedicalSciences,Mashhad, Iran KendraSorroza-Martínez InstitutodeInvestigaciones enMateriales, UniversidadNacional Autónoma deMéxico, Circuito Exterior CiudadUniversitaria, MéxicoCity,Mexico Suna Timur CentralResearch TestandAnalysisLaboratory ApplicationandResearch Center,Ege University,Bornova, Izmir,Turkey;Departmentof Biotechnology, GraduateSchoolof Naturaland AppliedSciences,Ege University,Bornova,Izmir,Turkey;Department of Biochemistry, Faculty ofScience,EgeUniversity, Bornova,Izmir,Turkey CHAPTER 1 Background of carbon nanotubes for drug delivery systems Mahdieh Darroudi1, Seyedeh Elnaz Nazari1, Prashant Kesharwani2, Majid Rezayi3,4,5, Majid Khazaei1,4 and Amirhossein Sahebkar6,7,8 1DepartmentofPhysiology,FacultyofMedicine,MashhadUniversityofMedicalScience,Mashhad, Iran;2DepartmentofPharmaceutics,SchoolofPharmaceuticalEducationandResearch,JamiaHamdard, NewDelhi,Delhi,India;3MedicalToxicologyResearchCentre,MashhadUniversityofMedical Science,Mashhad,Iran;4MetabolicSyndromeResearchCentre,MashhadUniversityofMedicalScience, Mashhad,Iran;5DepartmentofMedicalBiotechnologyandNanotechnology,SchoolofScience, MashhadUniversityofMedicalScience,Mashhad,Iran;6AppliedBiomedicalResearchCenter,Mashhad UniversityofMedicalScience,Mashhad,Iran;7BiotechnologyResearchCenter,Pharmaceutical TechnologyInstitute,MashhadUniversityofMedicalSciences,Mashhad,Iran;8Departmentof Biotechnology,SchoolofPharmacy,MashhadUniversityofMedicalSciences,Mashhad,Iran 1.1 Introduction Biotechnology researchers have developed a keen interest toward nano- technology and have been focusing on working with nanomaterials in recent decades [1,2]. Because of their unique properties, nanomaterials are particularly well-suited for biomedical applications. They are facile to synthesize, can be modified in size, contain tunable surface chemistry, providelargesurface-to-volumeratios,andaregenerallybiocompatible[3]. All of these features make nanomaterials promising for almost all aspects of biotechnology, overcoming the many shortcomings in existing conven- tional materials [4]. Following a pioneering study by Higuchi et al. on albumin nanoparticles, it was suggested that nanomedicine could be an effective tool to target tumors and cancer cells as the ability to avoid immune system clearance is enhanced [5]. Nanoparticles have shown to have positive results against coronary artery disease, and cancer cells, by effec- tively avoiding clearance from immune system clearance [6e9]. Nano- particles can be used to deliver a large variety of pharmaceuticals in a way that is safer (through targeted nanomedicines by limiting the amount of drug delivered) and more effective [10]. Biological and medical nanomaterials have been used for years, including liposomes [11], carbon nanoparticles [12e17], dendrimers [18], ceramic nanoparticles [19], iron oxide nanoparticles [20], titanium dioxide nanoparticles [21], magnetic nanoparticles, polymer nanocomposites [18], silica and metal nanoparticles [22]. Additionally, many different types of nanomaterials have been EmergingApplicationsofCarbonNanotubesinDrugandGeneDelivery ISBN978-0-323-85199-2 ©2023ElsevierLtd. https://doi.org/10.1016/B978-0-323-85199-2.00009-1 Allrightsreserved. 1 2 EmergingApplicationsofCarbonNanotubesinDrugandGeneDelivery proposed as means of drug/gene delivery that respond to external stimuli. In addition, drugs release from within these nanocarriers are triggered by changes in pH, redox potential, enzyme activation, thermal gradients, magnetic fields, light, and ultrasound [23]. Among the nanomaterials, carbon nanotubes (CNTs) have drawn tremendousinterestinthebiomedicalfieldbecauseofboththeirpromising properties, including high drug loading capacity [24], high stability [25], needle-like structure, high surface area [25], biocompatibility [26], flexible interaction with cargo, considerable strength, outstanding mechanical and electrical properties [27], and the ability to deliver drugs to specific tissues [28]. Despite the advantages, it also has some disadvantages related to toxicity and low biodegradability [29,30]. Although CNTs exhibit some undesirableproperties,theyarestillbeingutilizedinmedicineininnovative ways, such as in drug delivery systems, gene delivery, gene therapy, diag- nostic applications, as well as biosensors and vaccine delivery [29]. CNTs have a variety of appealing properties in biomedical applications, as shown in Table 1.1. Though CNTs have several desirable biological properties, their biosafetyisoftenanissueofconcern,particularlyinregardstotheiruseand theirbiomedicalapplications.Therefore,acomprehensiveassessmentofthe in vivo impact of CNTs is required before wide-scale commercial biomedical applications are undertaken. Studies on CNTs have been crit- icized for their inaccuracies and incompleteness, ranging from animal models that aren’t representative of human exposure routes to studies that lack even a thorough description of the impurities, chemistry, charge, and dimensionsofthestudiedCNTs[37].Graphenesheetsarerolledseamlessly as a cylindrical tube to form single-wall carbon nanotubes (SWCNT), as well as multi-walled carbon nanotubes (MWCNTs), which are composed of layers of graphene sheets stacked on one another. Moreover, there are three main methods for the manufacture of CNTs: chemical vapor depo- sition (CVD), laser ablation, and arc discharge [38]. In the current chapter book, we summarize promising and not-so-promising studies showing the importanceofCNTsinavarietyofbiomedicalapplications.Manyresearch studies,particularlyperformedinyear2016e2022,areassessedwithcritical insight into what these studies conclude. Herein, the uptake of CNTs, the delivery of pharmaceutical agents using CNTs has been covered. We also discuss concerns raised about the toxicology of CNTs at the end of this study and outline what and where the field urgently needs to grow. Backgroundofcarbonnanotubesfordrugdeliverysystems 3 Table1.1 Variousapplications ofcarbonnanotubes. Application Description References Diagnosing application Bioimaging Carbon nanotube’s optical, electronic and [31,32] and biosensing mechanical properties make it a promising material for the production of electrochemical and optical biosensors and some other applications deriving from CNTs because of their high photostability and lack of quenching Therapeuticalapplication Photothermal CNTs would produce heat by converting [33] therapy near-infrared radiation (NIR). Drug delivery The unique needle-like shape of carbon [34] nanotubes with the ability to quickly penetrate cell membranes makes them ideal carriers of drugs/genes due to their high surface area, multifunctional surface chemistry, lack of immunogenicity, and high surface area. Tissue Carbon nanotubes can be used in tissue [35] engineering engineering because of their biocompatibility, stiffness, mimicking of natural tissue nanofibers, cell adhesion and proliferation stimulation, and ability to form 3D structures. Lab-on-chip- Miniaturized systems such as lab-on-a-chip [36] devices devices are used to examine drugs, grow cells, and model diseases using tiny volumes of fluid flowing in various channels. The CNTs would be used in LOC devices as membrane channels, sensors, and channels walls. 1.2 Quantitative approaches Asignificantapplicationofnanoparticlesisthedeliveryofdrugs;becauseof theirlargesurfaceareas,nanoparticlesarecapableofdeliveringlargequantities ofdrugsorothermedicalcargos[39,40].Therefore,developingefficientdrug delivery systems is vital to human health [41]. Theranostic with nanotech- nology for cancer has emerged as a promising field that could integrate the 4 EmergingApplicationsofCarbonNanotubesinDrugandGeneDelivery treatment and diagnosis of cancer by combining nanotechnologies with therapeutic agents to enable targeted drug accumulation in cancer-specific cells without affecting normal cells [42]. Drug delivery procedures should besignificantlyimprovedtoensuresustainability,lowdisruptions,andprecise and accurate controlled delivery of drugs [43]. Nanomaterial-based drug deliverysystemshaverecentlybeenstudied,andanumberofbreakthroughs have been noted thereafter. There have been numerous studies on drug delivery systems in recent years [44,45]. The bibliometric is insufficient to assessaresearchareaoutputs;itshouldincludeotherinputssuchasliterature reviewstodiscovertheinsightofpublicationstrends[46].Thisresearchaims toexploretheresearchstatusdoneinthisfieldofstudyfrompasttothecurrent yearbyabibliometricapproachandqualitativeliteraturereview.Toensure the reliability of the analysis and input data for the software, scientometric studies utilizing recognized database such as Google Scholar, ISI Web of Science,andScopushavebeenaccessed.ThisstudyusedtheScopusdatabase foritsextensivecoverageandcomprehensivecontent. From 1965 to 2021, bibliometric searches were conducted in Google Scholar, Scopus, PubMed, and Web of Science Core Collections (n¼70,300). Data were obtained from the online version of the core collection in Web of Science on January 15, 2022 [47]. The “Carbon nanotube*”OR“CNT*”OR“SWCNT*”OR“MWCNT*”toidentify allarticlesrelatedtotreatmentfrom1990to2022thatcontainthekeyword in the title list, and 189,358 publications were encountered. Also, articles using the keyword “Drug Delivery*” AND “Carbon nanotube*” OR “CNT*” OR “SWCNT*” OR “MWCNT*” to identify all articles from 1990 to 2022 that contain the keyword in the title which, 4748 publications met the selection criteria. Upon further screening, only 3137 publications were categorized through “Drug Delivery*” AND “Carbon Nanotube*” OR “CNT*” OR “MWCNT*” OR “SWCNT*” key- words that were utilized for further analysis. Moreover, more data for this study basedon title search were derivedfrom SCOPUS, and thetime span was from 1985 to 7rd February 7, 2022. Also, bibliometric studies were carried out on the Google Scholar and PubMed databases, resulting in 70,300 publications and 1353 publications. This data collection with an initialtitlesearch“DrugDelivery*”inthe“TitleofArticle”hasbeendone on another well-known database Scopus [47]. There were almost 38,996 documents with the title of “Drug Delivery*”; and nearly 125,277 documents with the title of “Carbon Nanotube*” while the “CNT*” OR “MWCNT*” title search terms were used to retrieve the data. The search