\r\n\tEqually, the interlinkages that the adrenal gland has in the human body create the premises both for the description of the intimate mechanisms that induce adrenal diseases on other tissues and organs and also for strategic considerations when it comes to treatment.
\r\n
\r\n\tThis book, which is aimed at both endocrinologists and practitioners in other medical fields, therefore offers an insight into the mysteries of adrenal disease and a comprehensive overview of the current state of knowledge of this gland, providing an easy-to-follow format that focuses on the most important developments in the field of etiopathogenesis, clinical and paraclinical diagnosis, and treatment of these conditions.
",isbn:"978-1-80356-687-0",printIsbn:"978-1-80356-686-3",pdfIsbn:"978-1-80356-688-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"86c26879d83ac24206ed5476b6cde7fd",bookSignature:"Dr. Diana Loreta Paun",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11853.jpg",keywords:"Cushing Syndrome, Etiopathogenesis, Diagnosis, Treatment, Minimally Invasive Technique, Adrenalectomy, Adrenal Diseases, Perioperative Management, Adrenal Cancer, Genetics, Adrenal Mass, Imaging",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 22nd 2022",dateEndSecondStepPublish:"May 26th 2022",dateEndThirdStepPublish:"July 25th 2022",dateEndFourthStepPublish:"October 13th 2022",dateEndFifthStepPublish:"December 12th 2022",remainingDaysToSecondStep:"8 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Practitioner endocrinologist, associate professor, researcher, and manager of the National Institute of Endocrinology in Romania, coordinator of investment research and training projects, funded by European funds. Dr. Paun is a member of The Romanian Association of Clinical Endocrinology, member and president(2011-2012, 2017-2019) of The Romanian Chapter of the AACE (American Association of Clinical Endocrinologists). Dr. Păun was appointed State Advise (2015) and was appointed Presidental Advisor (2019).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"190860",title:"Dr.",name:"Diana Loreta",middleName:null,surname:"Paun",slug:"diana-loreta-paun",fullName:"Diana Loreta Paun",profilePictureURL:"https://mts.intechopen.com/storage/users/190860/images/system/190860.jpg",biography:"PĂUN DIANA LORETA, MD, PhD, FACE\r\nBorn on: February 1st, 1968 on Bucharest\r\nEmployed to: “Carol Davila”, University of Medicine and Pharmacy\r\nPosition: endocrinologist, Ph.D, Associate Professor of Endocrinology\r\nFellow of the American College of Endocrinology\r\nExperience: General Manager of “CI Parhon” Institute of Endocrinology, Bucharest, 2006-2015.\r\nMaster in Public Health\r\nQualifications in: Diabetology, Osteoporosis, Endocrine Ultrasonography, Public Health. Training in molecular biology laboratory techniques – Max-Planck-Institut für Psychiatrie, Dept. of Chemie u. Endokrinologie, München, 2002\r\nOccupational field: Clinical, Educational and Research activities, Management, Healthcare services.\r\nPostgraduate courses in: Informatics, Clinical Endocrinology, Infertility, Sexology, Public Health etc.\r\nProfessional career:\r\nChemistry-Biology High School graduated on 1986, Faculty of Medicine graduated on 1992, Th.Burghele Hospital doctor on probation during 1993–1994\r\nendocrinology resident to CI Parhon Institute of Endocrinology 1994-1998\r\nendocrinologist since 1998\r\nAssistant Professor, Lecturer, Associated Professor of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucuresti, Romania\r\nPublications: papers presented on national and international meetings, articles publishised in well-known journals, author and coauthor in monographs and clinical guides book.\r\nParticipation on research projects and clinical trials: Director and member of the team in research projects and in clinical trials.",institutionString:"Carol Davila University of Medicine and Pharmacy",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"455410",firstName:"Dajana",lastName:"Jusic",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/455410/images/20500_n.jpeg",email:"dajana.j@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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6. 1. Introduction
Up to now, many efforts have been made to produce smart materials with extraordinary properties usable in broad range of technological applications. In particular, within the last two decades, it has been demonstrated that properties of new prospective materials depend not only on their chemical composition but also on the dimensions of their building blocks which may consist of common materials [1,2].
A nanoparticle consists of a few atoms forming a cluster with size in the nanometer range. A nanometer represents a magical size of matter around which the vast majority of materials possess extraordinary, novel physico-chemical properties compared to its bulk form. Considerable attention has been focused during the last few decades on developing and optimizing methods for the preparation of gold nanoparticles to size and shape. Especially properties of 0D spherical and non-spherical particles, as applications of nanostructured materials, may differ considerably depending on the particle shape itself. Simple and straightforward example of the shape dependent behaviour of nanometer-sized particles is its colour. Ultrasmall gold spheres or clusters has been known for centuries as the deep red ruby colour of stained glass windows in cathedrals and domestic glassware. The colour results from the plasmon resonances in the metal cluster. Nowadays, most gold nanoparticles are produced via wet, chemical routes. Nevertheless, synthesis of metal nanoparticles (NPs) has been extensively studied since early 80’s [3-9]. Some pioneering works on synthesis of gold nanoparticles were even published as far back as in early 50’s by Turkevich [6]. Since that, many techniques have been developed, however, predominately based on wet, chemical processes [4-9]. Currently the most common noble-metal nanoparticle synthesis techniques are those developed by Brust-Shiffrin in 1994 [5]. The method based on reduction of AuIII+ complex compound with NaBH4 stabilized by thiols enables preparation of high stable particles with pretty narrow distribution and well-controlled size around 1 nm.
Besides interesting properties of nanostructured gold systems such as catalytic effects or magnetism [2,10], which both originate from surface and quantum size effects, they are also extremely usable those, which are closely connected with the average number of atoms in the nanoparticles. The properties and behavior of extremely small gold particles completely differ from those of bulk materials, e.g., their melting point [2,11,12], density [13], lattice parameter [13-15], and electrical or optical properties [13,14,16] are dramatically changed. Gold is also critical component in certain therapies, more specifically, in the treatment of cancer by hyperthermia and thermoablation. These two therapies use heat to kill cancer cells. In the case of hyperthermia, the cancerous tissue is heated to enhance conventional radiation and chemotherapy treatments, while in thermoablation the tissue is heated so that the cancer tissue is destroyed by the localised heat. In principle, there are two methods which can be used to provide heating, i.e. infra-red absorption and the application of an oscillating magnetic field to magnetic nanoparticles. Owing to this, nanosized gold is nowadays used in a vast range of cancer therapy applications such as cancer therapy agents [17] or cancer cell imaging [18,19]. Moreover, gold nanoparticles have often been conjugated with antibodies [20], or grafted to other carriers for surface property enhancement [21,22].
Besides above mentioned 0D nanostructures (nanodiscs, nanoparticles, nanoclusters) increasing efforts have been recently devoted also to one-dimensional (1D) nanostructures. 1D nanostructures in the form of wires, rods, belts and tubes have long been the focus of intensive research owing to their unique applications in mesoscopic physics and fabrication of nanoscale devices [23-25]. It is generally accepted that 1D nanostructures provide a good system for the investigation of the dependence of electrical and thermal transport or mechanical properties on dimensionality and size reduction (quantum confinement) [26]. Of the many elements and compounds from which nanowires may be made, gold is technologically important for its low electrical resistivity (2.21 μΩ cm) [27], its inertness to attack by air and its resistance to sulfur-based tarnishing [28]. Additionally, gold is more biocompatible than most metals, rendering it suitable for implantation [29,30] or electrical interfacing with cells [31,32] and tissues in nanobiological applications [33-35].
Nanostructured materials with high aspect ratios such as nanorods, nanowires, and nanoline patterns often exhibit anisotropic electronic and optical properties that differ from those observed in the bulk materials. These unique materials can be used to create many interesting devices, including fast responding chemical and biochemical sensors [36-40]. The high aspect ratio of nanowires should also make them interesting for the use in two dimensional photonic crystals, where vertical nanowires would constitute an array of high refractive index pillars in air [41]. Field emission from nanowires has also been reported [42], suggesting the possibility of devices such as field emission displays (FEDs) with nanowires acting as cathodes.
A variety of fabrication techniques have been developed in the past decade that yield high quality nanowires. Fabrication of ordered arrays of metallic nanoparticles supported on transparent substrate by sequential techniques like electron beam lithography has been demonstrated [43]. Such top-down approaches, however, are cumbersome and have a low yield, which hinders practical applications. High throughput approaches for the synthesis of metallic nanowires are thus intensely searched [44-48]. In general, the production of arrays of nanostructures on substrates by lithographic techniques presents the disadvantage of high cost and a restriction in the number of materials to which it can be applied. The method can also prove to be complex and inefficient. Template based methods overcome those disadvantages, but the obtained structures often present a high number of imperfections due to packing defects in the original templates [49].
Above mentioned applications, however, usually require gold nanostructures (0D or 1D) to be either suspended in colloid solution or attached to another support medium. Concerning this, creation of nanostructured gold directly on appropriate support may be technologically valuable since one can avoid additional preparation step oriented on metal-substrate mutual attachment. Therefore, this chapter focuses on new possible approaches for nanostructuring of gold layers either formerly deposited on solid substrates (polymer or glass) or during deposition itself (polymer). The formerly mentioned technique is based on the intensive post-deposition thermal annealing of sputtered layers on polytertaflouroethylene (PTFE) or glass, whereas the latter technique is based on forced (preferential) growth of gold on nanostructured polymer template. The method, combining nanoscale patterning of the polyethyleneterephtalate (PET) substrate by polarized light of excimer laser with glancing angle deposition of the gold, provides an interesting alternative to time consuming sequential lithography-based nanopatterning approaches.
First part of the text is focused on the study of selected physico-chemical properties of deposited gold layers and its changes induced by post-deposition annealing. The gold nanostructures of different thicknesses were sputtered onto glass or polymer (PTFE) substrate and then the samples were annealed from room temperature to 300°C. The effects of annealing on gold structures sputtered onto substrate, their surface morphology and roughness were studied using Atomic Force Microscopy (AFM), lattice parameter and crystallites size and their distribution by X-ray diffraction (XRD) and by SAXSess. Hall mobility, volume resistance and free carrier concentration were measured by Van der Pauw method, an electric permitivity by ellipsometry, an optical band gap by UV-Vis spectroscopy and a sheet resistance of gold nanostructures by 2-point method.
In the next part special attention will be given to the irradiation of PET surface with linearly polarized light of a pulsed KrF excimer laser to produce templates for preparation of laterally ordered self-organized arrays of metallic nanowires. Different fluences and angles of incidence of the laser beam were applied. The periodicity of the ripples created on the polymer surface was controlled by changing the incidence angle of laser light during irradiation. Subsequently the modified polymer surface was coated with gold using two deposition techniques (sputtering and evaporation). The surface of nano-patterned coated/uncoated PET was analyzed by AFM and a scanning electron microscopy equipped with a focused ion beam (FIB-SEM), allowing to cut cross-sections of the laser patterned substrate surface and the deposited gold layers
2. Gold nanostructures on glass substrate
An overview of growth process, morphology, electrical and optical properties of ultra-thin gold layers sputtered on glass is provided in following sections. Insight into the phenomena taking place during post-deposition thermal treatment is also given.
2.1. Thickness, morphology and inner structure
Thickness of sputtered layers was measured by AFM. Thickness in the initial stage of deposition (sputtering time less than 50 s) was determined from the SEM image of the sample cross-section (FIB-SEM). Dependence of the layer thickness on sputtering time is shown in Fig. 1. Linear dependence between sputtering time and structure thickness is evident even in the initial stage of the layer growth. This finding is in contradiction with results obtained earlier for Au sputtering on PET [50]. In that case, the initial stage of the layer growth was related to lower deposition rate which is due to different morphology.
Figure 1.
Dependence of the gold structure thickness on sputtering time [13].
In Fig. 2, a SEM picture of the cross-section of the Au layer at its initial stage of growth is shown. It is obvious that after approximately 20 s of Au deposition, flat, discrete Au islands (clusters) appear on the substrate surface. The flatness may indicate preferential growth of gold clusters in a lateral direction. When the surface coverage increases and the clusters get in close contact with each other, a coarsening sets in and becomes the dominant process. After the surface is fully covered, additional adsorption causes only the vertical layer growth, while the lateral growth is dominated by cluster boundary motion [51].
Figure 2.
SEM scan of the FIB section of gold structure on glass substrate. Deposition time was 20 s. [13].
The AFM images that illustrate the surface morphology and roughness (Ra) of gold-coated glass before and after annealing are shown in Fig. 3. For the sake of comparison only images of the samples with identical vertical scale were chosen. From Fig. 3 it is clear that the surface morphology of the as-sputtered structures does not depend significantly on the sputtering times. Monotonous decrease of surface roughness with deposition time is related to the stage of the layer growth. During initial stages of metal growth the layer is formed over isolated islands. After that, during ongoing deposition, interconnections between clusters are formed and the deposited layers become homogeneous and uniform. Decrease of surface roughness is direct evidence of the formation of a thicker layer during sputtering process on flat substrate. After annealing, however, the surface morphology changes dramatically. Similar changes in the morphology of the thin gold structures have also been observed on the samples annealed at 200°C for 20 hours [52] and at 450°C for 2 hours [11]. It is seen from Fig. 3 that the annealing leads to the formation of “spherolytic and hummock-like” structures in the gold layers. The formation may be connected with an enhanced diffusion of gold particles at elevated temperature and their aggregation into larger structures. It is well known that the melting point of the gold nanoparticles decreases rapidly with decreasing particle size [2,11,12].
The migration of the gold nanoparticles and formation of larger structures may be connected with lower thermodynamic stability of the gold nanoparticles and lower gold wettability of glass. This idea is supported by some previous XRD experiments in which dominant (111) orientation of gold crystals in the sputtered gold layers was determined [11, 53]. The (111) oriented gold crystals are known to be thermodynamically unstable and their melting and cracking starts from the edge parts that should be bounded to Au (110) surface [11].
Metallic nanoparticles and generally nanostructures composed of metals often exhibit different values of structure parameters compared to their bulk form e.g. contraction of lattice parameter in nanostructures increases material density [13,53]. Lattice parameters a of the face-centered cubic gold nanostructures determined before and after annealing are shown in Fig. 4 as a function of the sputtering time (i.e. effective layer thickness). Lattice parameters were calculated using the Rietveld procedure (full pattern fitting). For this purpose the five strongest diffraction lines were taken into account. For very thin films the diffraction lines are weak and the resulting values of the lattice parameters are loaded by a higher error. The error is especially large for the as-sputtered samples. A dramatic difference is found in the dependences of the lattice parameter on the sputtering time between as-sputtered and annealed samples. For as-sputtered samples the lattice parameter varies rapidly with the increasing sputtering time, i.e. with the increasing mean size of the gold crystallites [16,53,54]. It is seen that a maximum lattice parameter is observed after 100 s of sputtering, i.e. for the layer thickness of about 18 nm. For both the thinner and thicker layers the lattice parameter declines significantly. The same trend in the lattice parameter vs. sputtering time dependence was reported also for silver structures, for which the lattice parameter increases slightly up to the structures size of 12 nm and then decreases [55]. In contrast to the as-sputtered gold structures at the annealed ones the lattice parameter is nearly independent on the sputtering time and the size of the structures.
Figure 3.
AFM scans of gold structures sputtered for 75, 200 and 400 s on glass substrate before (RT) and after annealing (300°C). Ra is the average surface roughness in nm [16].
Figure 4.
Dependence of the gold lattice parameter on the sputtering time (i.e. effective thickness) measured before (-●-) and after annealing at 300°C (-■-)[14].
The dependence of the crystallite size on the sputtering time before and after annealing is shown in Fig. 5. The dependences are quite different for the as-sputtered and annealed samples. While in the as-sputtered samples the crystallite size is amonotonously increasing function of the sputtering time, in the annealed ones the crystallite size first increases rapidly up to the sputtering time of 250 s, achieves a maximum and then it decreases. A dramatic increase of the Au crystallite size with the annealing temperature was published also by Santos et al. [56].
Size distribution of the Au crystallites determined by SAXSess method is presented in Fig. 6. The mean crystallite size values (modus) determined by SAXSess (S) and by XRD (X) are compared in Fig. 5. It is obvious that before annealing both methods (SAXSess, XRD) give the same values of the mean crystallite size, which increase slightly with the deposition time. Both SAXSess and XRD measurements prove dramatic increase of the mean crystallite size after annealing. However, there is an obvious dissimilarity between SAXSess and XRD results regarding longer sputtering time which is caused by inability of the SAXSess method to examine crystallites larger than ca 90–100 nm. The different behavior may be due to a crystallites’ re-crystallization in the annealing process. The crystallite size determined by the XRD technique is based on the determination of the so-called coherently diffracting domains with their mean dimensions in direction perpendicular to the film surface. This is the reason why the crystallites determined in this way significantly exceed their size in some cases.
Figure 5.
Dependence of the size of the gold crystallites on the sputtering time (i.e. layer effective thickness) measured before (-○- S, -●- X) and after annealing at 300°C (-□- S, -■- X) using S – SAXSess, X – XRD methods [14].
Figure 6.
Pair distance distribution functions (PDDF) of gold crystallites by different sputtering time (in seconds) before (solid line) and after annealing (dashed line) measured by SAXSess method [14].
2.2. Optical and electrical properties
Besides interesting catalytic and electronic properties, nanoparticles of noble metals exhibit also distinctive, shape-dependent optical properties that have attracted great technological interest. This is particularly true for gold nanostructures [11]. Images of the sample surface for different sputtering times and for sputtered and annealed samples are shown in Fig. 7.
Figure 7.
Images of the glass samples with gold structures sputtered for increasing times. The as-sputtered (RT) and annealed samples (300°C) are shown for comparison [16].
The deposited samples become darker with increasing sputtering time, the darkening being related to increasing thickness of the gold structures. Also a gradual change of the structures colour from blue to green is seen. After annealing all structures exhibit reddish colour, regardless of the sputtering time. The changes in the layer colour indicate pronounced alteration in the gold nanostructure caused by the annealing (see Fig. 3). It could be in accordance with previously presented results, the small gold sample about 10 nm absorbs green light and thus appears red [2]. This effect was confirmed also by UV-Vis spectroscopy. For the sake of clarity only some of UV-Vis spectra from as-sputtered and annealed samples are shown in Fig. 8 (RT and 300°C). The absorbance of gold structures increase with increasing sputtering time and structure thickness as could be expected. From comparison of the spectra of the sputtered and annealed samples it is seen that the annealed structures have qualitatively different shapes and lower absorbance. Both phenomena point at structural changes due to annealing. The observed shift of the 530 nm absorption peak (corresponding to surface plasmon resonance) with increasing sputtering time towards longer wavelengths is probably related to interconnection and mutual interaction of gold nanosized islands in the structure. From present UV-Vis spectra it is evident that the as-sputtered samples prepared for deposition time of 30 s and that annealed one (sputtering time 200 s) are the first ones, which do not exhibit the peak of plasmon resonance. Qualitative difference between absorbances of the sputtered structure and that annealed may indicate a transition from the structure comprising discrete gold islands to continuous gold coverage.
The UV-Vis spectra were also interpreted in the frame of the well-known Tauc’s model [57] and the optical band gap (Egopt) was calculated as a function of the sputtering time for sputtered and annealed samples. This dependence is shown in Fig. 9. Also the gold structure thickness vs. sputtering time measured by AFM method on the scratch step is presented. These values, inclusive the result that the AFM-scratch technique is not applicable on annealed structures due to their altered morphology, were taken from our previous work [53]. It is seen from Fig. 9 that the structures sputtered for times below 150 s exhibit non-zero Egopt. Rather dramatic change in the Egopt is observed after annealing, where the values of the Egopt are much higher in comparison with those of the sputtered sample. For samples sputtered for times around 300 s a non-zero Egopt is observed. For behaviour of ultra-thin metal structures (<10 nm) the surface-size and quantum-size effects must be considered [2,53,58]. This quantum-size effect in small structures leads e.g. to a semi-conducting character, which is accompanied by non-zero Eg (band gap) or Egopt. This effect was observed in the present case.
Figure 8.
UV-Vis spectra of gold structures sputtered on glass before (RT) and after annealing (300°C). The numbers in Figs. are sputtering times in s [16].
The dependence of the volume resistivity on the sputtering time is seen from Fig. 10a. For as-sputtered samples a rapid drop of the resistivity over a narrow thickness interval is observed. The drop indicates a transition from electrically discontinuous to continuous gold coverage. For annealed samples the resistivity drop is shifted towards thicker layers. The difference is obviously connected with changes in the layer structure taking place during annealing i.e. gold coalescence and formation of isolated islands [16]. The onset of the rapid resistivity drop is observed after 50 and 150 s of sputtering for as-sputtered and annealed samples, respectively. Free carrier volume concentration and their Hall mobility significantly affect the electrical conductance of materials. The dependence of the free carrier concentration and the mobility on the sputtering time is shown in Figs. 10b and 10c, respectively. As can be seen from Fig. 10b, with increasing sputtering time the carrier concentration increases dramatically and the layers become conductive (see Fig. 10a). As in the case of resistivity the onset of the rapid increase of the free carrier concentration on annealed samples is shifted towards longer sputtering time. Thus the constant level of the free carrier concentration is achieved later compared to the as-sputtered samples. A similar dependence of the free carrier concentration on the layer thickness was recently observed on PET and PTFE sputtered with gold [59]. The carrier mobility also changes dramatically with increasing sputtering time for non-annealed and annealed samples (Fig. 10c). The mobility first declines rapidly to a point when an electrically continuous layer is formed. The decline may be due to the fact that in a discontinuous layer the mobility mechanism differs from classical electron conductivity common in metals. For annealed structures the continuous layer is formed after a longer deposition time. For thicker, electrically continuous gold layers the mobility is a slowly increasing function of the sputtering time.
Figure 9.
Dependence on the sputtering time of the optical band gap of gold structures before (RT) and after annealing (300°C) (-□- for RT and -■- for 300°C) and thickness (-○-) [16].
There is a clear correspondence between mobility (Fig. 10c), free carrier volume concentration (Fig. 10b) and volume resistivity (Fig. 10a). A similar dependence of the free carrier concentration on the thickness of the gold layers deposited by sputtering on PET and PTFE was observed [59]. Simple and straightforward interpretation of the above described observations is that during electrical measurement on discontinuous gold layers an electron injection due to the tunneling effect occurs [13,16]. With ongoing deposition time the discrete structures become interconnected and form an electrically continuous, homogeneous layer in which the concentration of free carriers is saturated.
Figure 10.
Dependence of the volume resistivity (A), surface free carrier volume concentration (B) and surface free carrier Hall mobility (C) on the sputtering time measured by van der Pauw technique before (-●-) and after annealing at 300°C (-■-) [14].
The IR part of optical constants of the as-deposited and annealed Au films determined from ellipsometry also supports the results of electrical transport measurements. Fig. 11 presents the real part of electric permittivity in the studied spectral range.
Spectroscopic features in the Drude (IR) region clearly show the tendency of Au films to lose their metallic behavior with decreasing thickness due to gold coalescence, leading to a layer discontinuity [16]. Film discontinuity of the as-deposited thin layers is a natural consequence of the mechanism of the layer growth. Percolation threshold is reached at the layer thickness of about 7 nm [60] corresponding to the deposition time of about 25 s in the present case. Fig. 11 also shows that the strong change in the surface morphology induced by the annealing shifts the metal-to-insulator transition towards greater layer thicknesses (i.e. deposition times). The thickness variation of IR end of the real part of the electric permittivity spectra of annealed gold layers (positive value reaching the maximum and then passing through zero to negative values with increasing deposition times) is consistent with previous studies of metallic films around the percolation threshold [60]. For the annealed layers with sputtering times equal to or smaller than those corresponding to the metal-to-insulator transition, a strong signature of plasmons is expected in the VIS part of optical constants. This is documented in Fig. 12, where the spectral dependence of the imaginary part of the electric permittivity is shown.
Figure 11.
Real part of the electric permittivity spectra of as-sputtered (RT, upper part) and annealed (300°C, lower part) gold structures obtained by spectroscopic ellipsometry for the different sputtering times [14].
Plasmon oscillator band for the layer sputtered for 50 s is centered at around 2.3 eV (540 nm). With increasing deposition time the band becomes broader and shifts to longer wavelengths (lower photon energy). For 200 s sputtering time the plasmon band splits into two and for longer sputtering times it integrates into the Drude term in the IR spectral limit. This change in the optical constants around the metal-to-insulator transition is the reason for the color variation of the annealed layers.
Figure 12.
Imaginary part of the electric permitivity spectra of annealed (300°C) gold structures. The presence and evolution of the plasmon bands should be noted (for details see the text). Coloured sign of curves is the same as in Fig. 11 [14].
The temperature dependence of the sheet resistance for two particular structure thicknesses is displayed in Fig. 13. One can see that the temperature dependence of the sheet resistance strongly depends on the structure thickness. For the layer about 89 nm thick, the resistance is an increasing function of the sample temperature, the expected behavior for metals. For the structure about 6 nm thick, the sheet resistance first decreases rapidly with increasing temperature, but above a temperature of about 250 K, a slight increase in resistance is observed. The initial decrease and the final increase of the sheet resistance with increasing temperature are typical of semiconductors and metals, respectively. It has been referred elsewhere [2] that a small metal cluster can exhibit both metal and semiconductor characteristics just by varying the temperature. It is due to temperature-affected evolution of band gap and density of electron states in the systems containing low number of atoms.
From the present experimental data, it may be concluded that for the thicknesses above 10 nm, the sputtered gold layers exhibit metal conductivity. In the thickness range from 5 to 10 nm, the semiconductor-like and metal conductivities are observed at low and high temperatures, respectively. Our further measurements showed that the layers thinner than 5 nm exhibit a semiconductive-like characteristic in the whole investigated temperature scale. Except for band gap evolution theory, typical semiconductor-like behavior may also originate from the tunneling effect of electrons through the discontinuous, separated Au clusters during electrical measurements. Since the probability of electron tunneling depends on the temperature, similarly, typical course of sheet resistance and, as will be shown later, CV characteristic may be affected right by this phenomenon.
Figure 13.
Temperature dependence of the sheet resistance for two different structure thicknesses indicated in the figure [13].
From presented measurements of sheet resistance results the semiconductor-like character of Au at specific structure conditions (thickness, temperature). The observed semiconductor-like character (decreasing resistance with increasing temperature) of ultrathin Au structures may originate from two undistinguishable phenomena. The first one results from a tunneling effect which occurs at discontinuous structures during resistance measurements [59]. The second one originates from the semiconductor characteristic of the intrinsic cluster itself, which occurs in metal nanostructures of sufficiently small proportions [2].
3. Gold nanostructures on polymeric substrate
In this section special attention is given to the changes in surface morphology and other physico-chemical properties of gold nanolayers, sputtered on polytetrafluoroethylene (PTFE) surface induced by post-deposition annealing.
3.1. Electrical properties
The dependence of the electrical sheet resistance (Rs) of the gold layer on its thickness before and after annealing (at 100, 200 and 300°C) is shown in Fig. 14. For the as-sputtered samples the sheet resistance decreases rapidly in the narrow thickness range from 10 to 15 nm when an electrically continuous gold coverage is formed. The resulting sheet resistance is saturated at a level of aproximately 200 Ω. From the measured Rs and effective layer thickness, layer resistivity R (Ohm centimeter) was calculated, which appears to be few orders of magnitude higher than that reported for metallic bulk gold (RAubulk = 2.5 × 10−6 Ω cm [61], e.g., for 100 nm thick Au layer RAu100 nm = 1 × 10−3 Ω cm). As in the case of Au coated glass substrate (see section 2), the higher resistivity of thin gold structures is due to the size effect in accord with the Matthiessen rule [62]. Annealing at temperatures below 200°C causes only mild shift in the resistance curve towards thicker layers. Transition from electrically discontinuous to electrically continuous layer in case of low temperature annealed samples is more gradual and occurs between the effective layer thicknesses from 10 to 20 nm regarding the annealing temperature. After annealing at 300°C a dramatic change in the resistance curve is observed. The annealed layers are electrically discontinuous up to the Au effective thickness of 70 nm above which the continuous coverage is created and a percolation limit is overcome. However, for longer sputtering times up to 550 s, the sheet resistance changes slowly and it achieves a saturation which is observed on the as-sputtered layers and layers annealed at low temperatures.
Figure 14.
Dependence of the sheet resistance (Rs) on Au layer thickness for as-sputtered samples (RT) and the samples annealed at 100, 200 and 300°C [63].
Compared to electrical properties discussed in chapter 2 (Au layers on glass substrate), one can see that in case of PTFE substrate the transition from electrically discontinuous to continuous layer is shifted towards thicker layers. This fact is due to incomparable value of surface roughness of substrate used which is in the case of PTFE one order of magnitude higher (see section 3.3).
3.2. Chemical composition
Besides the sheet resistance measurements, information on the layer structure and homogeneity can be obtained in another way too. Here, complementary information on the layer homogeneity is obtained from XPS spectra. Fig. 15 A,B shows intensity normalized XPS spectra (line Au 4f) of 20 and 80 nm thick sputtered gold layers, respectively. Black line refers to as-sputtered layer and blue line to the one annealed at 300°C. Annealing of the 80 nm thick gold layer does not change the XPS spectrum. In contrast, the annealing of the 20 nm thick layer results in strong broadening of both lines which is due to the sample charging in the course of the XPS analysis. The charging is closely related to the change in the layer morphology: from electrically continuous one for as-sputtered sample to discontinuous one after the annealing procedure [16]. This observation is in agreement with above described results of the sheet resistance measurements (see Fig. 1, section 3.1).
Figure 15.
Intensity normalized XPS spectra (line Au (4f)) of 20 (A) and 80 nm (B) thick sputtered Au layers on PTFE before (black line) and after (blue line) annealing at 300°C [63].
Concentrations of chemical elements on the very sample surface (accessible depth of 6 to 8 atomic layers) determined from XPS spectra are summarized in Table 1. The XPS data were obtained for the samples with 20 and 80 nm thick gold layers, both as-sputtered and annealed at 300°C. Total carbon concentration and the carbon concentration coming from PTFE (calculated from XPS data) are shown in columns 1 and 2 of the table, respectively. Major part of the carbon is due to sample contamination. Fluorine to PTFE carbon ratio F/CPTFE is close to that expected for PTFE (about 2). By the annealing at 300°C, the ratio decreases to 1.7 for both layer thicknesses. The decrease may be due to reorientation of polar C-F groups induced by thermal treatment. Oxygen detected in the samples may result from oxygen incorporation during gold sputtering which may be accompanied by partial degradation and oxidation of PTFE macromolecular chain or degradation products. Subsequent annealing leads to reorientation of the oxidized groups toward the sample bulk and corresponding decrease of the surface concentration of oxygen. The same effects have been observed earlier on plasma-modified polyolefines [64]. It is also evident from Table 1 that annealing causes resorption of contamination carbon both hydrogenated and oxidized one [65]. Changes in the morphology of the gold layer after the annealing are manifested in changes of the gold and fluorine concentrations as observed in XPS spectra. After the annealing, the observed gold concentration decreases and fluorine concentration increases dramatically, these changes clearly indicate formation of isolated Au islands similar to those in case of Au-coated glass substrate [16].
Au layer
Temperature
Atomic concentrations of elements in at. %
Thickness
C
CPTFE
O
Au
F
F/CPTFE
20 nm
RT
43.5
4.4
6.5
41.6
8.5
1.93
300°C
37.8
34.8
0.4
3.4
58.4
1.68
80 nm
RT
41.0
3.1
4.4
48.6
6.0
1.94
300°C
36.8
27.2
1.2
14.8
47.2
1.74
Table 1.
Atomic concentrations (in at. %) of C (1s), O (1s), Au (4f) and F(1s) in Au sputtered PTFE samples with Au effective thickness 20 and 80 nm after deposition (RT) a after annealing (300°C) measured by XPS. CPTFE represents calculated concentration from XPS data of carbon (in at. %) originating from PTFE only, F/CPTFE stands for fluorine to PTFE carbon ratio [63].
3.3. Surface properties and morphology
Another quantity characterizing the structure of the sputtered gold layers is zeta potential determined from electrokinetic analysis. Dependence of zeta potential on the gold layer thickness for as-sputtered samples (RT) and annealed samples at 300°C is shown in Fig. 16. For as-sputtered samples and very thin gold layers, the zeta potential is close to that of pristine PTFE due to the discontinuous gold coverage since the PTFE surface plays dominant role in zeta potential value. Then, for thicker layers, where the gold coverage prevails over the original substrate surface, the zeta potential decreases rapidly and for the thicknesses above 20 nm remains nearly unchanged, indicating total coverage of original substrate by gold. For annealed samples, the dependence on the layer thickness is quite different. It is seen that the annealing leads to a significant increase of the zeta potential for very thin layers. This increase may be due to thermal degradation of the PTFE accompanied by production of excessive polar groups on the polymer surface, which plays the important role when the gold coverage is discontinuous. Moreover, the surface roughness increases at this moment too (see Table 1 and Fig. 17 below) [66]. Then, for medium thicknesses, ranging from 20 to 70 nm, the zeta potential remains unchanged and finally it decreases again for higher thicknesses due to the formation of continuous gold coverage. It appears that the results of electrokinetic analysis (Fig. 16) and measurement of the sheet resistance (Fig. 13) are highly correlated.
Figure 16.
Dependence of zeta potential on the Au layer thickness for as-sputtered samples (RT) and the samples annealed at 300°C [63].
Figure 17.
AFM images of pristine (PTFE) and Au coated (PTFE/Au) samples (thickness of 20 nm) before (RT) and after annealing at 300°C. Numbers in frames are measured surface roughnesses Ra in nm [63].
The rapid decrease in the sheet resistance occurs at the same layer thickness as the decrease in zeta potential. Both correlated changes are connected with creation of continuous, conductive gold coverage. Another interesting fact is that even for the layers with thicknesses above 80 nm, the values of the zeta potential measured on as-sputtered and annealed samples differ significantly. This can be due to higher fluorine concentration in the annealed samples and the fact that the C-F bond is more polar and exhibits higher wettability. It should be also noted that the value of the zeta potential may be affected by the surface roughness too. In general, it follows that the thicker the gold coverage the lower the zeta potential is, reflecting the electrokinetic potencial of metal itself.
The changes in the surface morphology after the annealing were studied by AFM. AFM scans of pristine and Au-coated (20 nm) samples before and after annealing are presented in Fig. 17. One can see that the annealing causes a dramatic increase in the surface roughness of the pristine polymer. Since the annealing temperature markedly exceeds PTFE glassy transformation temperature (TgPTFE = 126°C) the increase in the surface roughness is probably due to thermally induced changes of PTFE amorphous phase. The gold sputtering leads to a measurable reduction of the sample surface roughness. The reduction may be due to preferential gold growth in holes at the PTFE surface. Annealing of the gold-coated sample leads to significant increase of the surface roughness too. In this case, the increase is a result of both, the changes in the surface morphology of underlying PTFE and the changes in the morphology of the gold layer. After annealing, the surface roughness of pristine and gold-coated samples is practically the same. This finding is in contradiction with similar study accomplished on gold layers deposited on glass substrate [16]. Possible explanation of this fact probably lies in much better flatness of the glass substrate and in lower thermal stability of PTFE substrate during annealing.
4. Self-organized gold nanostructures
Purpose of this section lies in description of phenomena taking place during both interaction of polarized laser light with the surface of polymeric material and its subsequent coating by metal. It will be shown that modification of the polyethylenetherephtalate (PET) surface with linearly polarized light from pulsed KrF laser has a significant effect on the properties of subsequently deposited gold nanolayers and the choice of the deposition technique is crucial owing to the quality of prepared coatings.
4.1. Surface morphology and structure parameters
It has been shown [67] that by the KrF laser irradiation with several thousand of pulses a periodic ripple structure is formed at a PET surface for a fluence range from about 4.2 to 18.8 mJ cm−2. The ripples have a fluence-independent width Λ, which is given by the formula Λ = λ/(1 – sin(θ)), Eq. (1) [68], where λ is wavelength of a laser light used, n the effective refractive index of material, and θ the angle of incidence. Fig. 18 displays AFM images of pristine PET and PET irradiated at different laser fluences. The sample irradiated with the laser fluence of 3.4 mJ cm−2 exhibits a rougher surface than the flat un-irradiated pristine PET. There is a noticeable modulation, although no ripple formation is visible. At higher laser fluences periodic ripple structures have developed in the irradiated area. At a laser fluence of 6.6 mJ cm−2, a regular and uniform coverage of the PET surface with ripples is reached. These results are based on AFM measurements, as those shown in Fig. 18. There is a good correlation between height and surface roughness of ripples over the whole laser fluence range shown in the figure. Both parameters reach the maximum value at a fluence of 6.6 mJ cm−2, which corresponds to a ripple height of about 90 nm.
Figure 18.
AFM images of the PET irradiated at different KrF laser fluences; the numbers in the inset refer to the laser fluence in mJ cm−2 employed for irradiation of the PET foils, while pristine stands for unirradiated pristine PET [70].
The height and the roughness of the ripples as a function of the applied laser fluence are shown in Fig. 19.
Figure 19.
Dependence of the ripple height (○) and roughness (□) on the KrF laser fluence employed for the PET irradiation [70].
Fig. 20 shows AFM images of the PET irradiated under different incidence angles of the laser beam. For larger angles of incidence, the spacing between two neighboring ripples is wider. For the incidence angle of 0° and 22.5°, the observed spacing of the ripples is in good agreement with the value calculated by Eq. (1) with an effective index of refraction n ≈ 1.2. The agreement for the incidence angle of 45° is less pronounced. The discrepancy may be due to changes of the polymer refractive index induced by the UV laser irradiation as reported earlier [69].
Figure 20.
AFM images of the PET irradiated at a KrF laser fluence of 6.6 mJ cm−2 under the different incidence angle of laser beam (0, 22.5 and 45°). The numbers in the insets in the upper left corner refer to the angle of incidence of the laser beam and in the insets in the upper right corner to the ripple period in nm [70].
FIB cuts of laser irradiated and gold coated PET samples were investigated by SEM (see Fig. 21). After sputtering, the gold is deposited in the form of “nanowires”, which grow mainly at the ridges of the ripples. The FIB cuts reveal that there could be gaps between the individual wires and that the metal layer may be discontinuous. The width of the gold nanowires directly correlates to the width of the ripples formed before gold deposition. Additionally, a granularity is visible along the wires, but the FIB cut images suggest that the grains may be interconnected. The morphology of the gold layers deposited by evaporation is distinctly different. The gold is also deposited in the valleys of the ripple structure.
Figure 21.
FIB-SEM images of the gold coatings on PET samples irradiated by a KrF laser under incidence angles 0 and 22.5° (fluence 6.6 mJ cm−2). The gold deposition was performed either by sputtering (Sputt.) and evaporation (Evap.) [70].
The nanowire structure of the sputtered gold layer can be observed also after gold deposition onto PET samples irradiated by the laser under an angle of incidence of 45°. Again, the evaporation of gold leads to a continuous coverage copying nanostructured polymer surface. The reason for the different observed gold morphologies after sputtering (nanowires) and evaporation (homogeneous gold coverage) is still unclear. The different particle energies in both processes are one possible reason. For sputtering, the particle energy may be considerably higher because of sample charging effect¸ while the evaporated materials should be slower (i.e., colder) and closer to thermodynamical equilibrium. The electrical charge of the sputtered particles can have also direct influence on layer formation, while the evaporated material should be mainly neutral. Other reasons may be the different deposition rates, which were a factor of two lower for sputtering than for evaporation, and possible differences of the substrate and gold layer temperature during the deposition in the two different techniques.
5. Summary
In summary, this chapter gives a comprehensive insight into the problematic of ultrathin gold films formed by physical deposition techniques on glass and polymeric substrates. Particular emphasis is given to the processes taking place during post-deposition annealing of prepared layers. In the case of glass substrate, the sputtering times and the layer effective thicknesses were chosen to span the region of the transition from discontinuous to continuous gold layer. For short sputtering times electrically discontinuous layers are obtained comprising discrete gold crystallites. The crystallite size in the as-sputtered samples is a monotonously increasing function of the sputtering time. The dependence of the lattice parameter of the gold crystallites forming the layer on the sputtering time is rather complicated with a rapid increase for shorter sputtering times and subsequent decrease for longer sputtering times. The decrease can be explained by relaxation processes in the thicker layers. The annealing has significant influence on the properties of the gold layers. For the annealed samples the lattice parameter practically does not depend on the sputtering time. The crystallite size first increases rapidly up to the sputtering time of 250 s, achieves a maximum and then decreases. The electrical properties (concentration, mobility of charge carriers and volume resistivity) and NIR optical properties of the gold layers change dramatically as the function of the sputtering time. Other significant changes, especially for electrically discontinuous layers, are observed as a result of the annealing. This is probably due to the different mechanism of free charge carrier transport, where also the quantum surface effects could be present in case of observed island structure mainly after annealing. For electrically continuous layer the concentration and the mobility are invariable. Similar behaviour exhibits also gold layers on polymeric substrate. From the measurement of the sheet resistance the transition from discontinuous to continuous gold coverage was found at the layer thicknesses of 10-15 nm for as-sputtered samples. After annealing at 300°C the transition point increases to about 70 nm, the increase indicating substantial rearrangement of the gold layer. The rearrangement is confirmed also by XPS measurement and an electrokinetic analysis. By XPS measurement contamination of the gold coated PTFE samples with carbon and the presence of oxidized structures, created during gold sputtering were proved. The annealing results in significant increase of the surface roughness of both pristine and gold sputtered PTFE.
Modification of the PET surface with linearly polarized light from pulsed KrF laser has a significant effect on the properties of subsequently deposited gold nanolayers and the choice of the deposition technique is crucial owing to the quality of prepared coatings. Subsequent deposition of 200 nm thick gold layer caused a decrease of the surface roughness. While by evaporation a continuous metal coverage is formed, copying nanostructured polymer surface, in the case of sputtering a nanowire-like structure of the gold coating can be observed. It was shown that the width of the nanowires can be tailored by the width of the ripples formed by preceding laser irradiation. We demonstrate a technique for the controlled patterning of polymer surfaces, including the creation of nanopatterned, regular gold structures (nanowires). In principle, this technique could be employed for the creation of metal-polymer composites with interesting electrical, mechanical, and optical properties, which could find novel applications in micro and nanotechnology.
Acknowledgement
Financial support of this work from the GACR projects No. P108/11/P337, P108/10/1106 and 106/09/0125 is gratefully acknowledged.
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Introduction",level:"1"},{id:"sec_2",title:"2. Gold nanostructures on glass substrate",level:"1"},{id:"sec_2_2",title:"2.1. Thickness, morphology and inner structure",level:"2"},{id:"sec_3_2",title:"2.2. Optical and electrical properties",level:"2"},{id:"sec_5",title:"3. Gold nanostructures on polymeric substrate",level:"1"},{id:"sec_5_2",title:"3.1. Electrical properties",level:"2"},{id:"sec_6_2",title:"3.2. Chemical composition",level:"2"},{id:"sec_7_2",title:"3.3. Surface properties and morphology",level:"2"},{id:"sec_9",title:"4. Self-organized gold nanostructures",level:"1"},{id:"sec_9_2",title:"4.1. Surface morphology and structure parameters",level:"2"},{id:"sec_11",title:"5. 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1. Introduction
Neglected tropical diseases (NTDs) include a collection of chronic, disabling, and physically disfiguring infectious diseases that usually affect dwellers of poor rural populations in tropical and sub-tropical countries of the world [1]. Apart from their negative impact on the health of victims, NTDs exert an immense socio-economic burden on the society as a result of the social stigma and physical disabilities associated with them. These interrelated negative outcomes perpetuate a cycle of poverty and unproductivity resulting in a consistent decline in economic growth [2]. As a major element of the Millennium Development Goals (MDGs), much effort is being put in for the elimination of the NTDs [3].
Among the NTDs, helminth infections especially soil-transmitted helminthiasis (STHs) and schistosomiasis are among the most prevalent afflictions of humans [4]. About 2 billion people are estimated to suffer from helminth infections worldwide, out of whom 300 million suffer from severe morbidity [5]. The negative impact of helminth infections on human growth and development (including cognitive development in childhood and nutritional status), pregnancy and work performance cannot be overemphasized. Though considered as acute health problems in some developed parts of the world, chronic parasitic infections are common and recurrent in poor communities and usually result in long-lasting complications making them a significant health threat to the populations who are continuously at risk for infection [6].
Over the years, many highly effective chemotherapeutic agents have been developed for treating helminth infections. Unfortunately in the setting of rural poverty where these diseases are mostly prevalent, access to healthcare facilities and the cost of medications are a challenge [7, 8]. Additionally, environmental factors and unavoidable domestic or occupational exposures, strongly favor the process of re-infection even after a successful therapy [9, 10]. Given that these infections also require lengthy treatment regimens with related costs which cannot be afforded by the affected victims, many patients seek for alternative treatment options especially the use of herbal medicines which are readily available and less expensive [9, 11].
Herbal extracts have been used in traditional medicines since ancient times for the effective treatment of human diseases [12]. Ethnobotanical studies in various regions of the world have documented medicinal plants used for the treatment of various parasitic infections. Scientific investigations of selected plants have also revealed remarkable activity of medicinal plants against specific human parasites [13, 14]. In Ghana, numerous medicinal plants play an important role in the healthcare system of rural communities. The Ghanaian flora provides a ready source for new therapeutic interventions for the local population [15, 16, 17]. This chapter provides a review with special focus on medicinal plants collected from Ghana with anthelmintic and anti-schistosomal activity.
1.1 Soil transmitted helminthiasis (STH)-the disease burden and current chemotherapy
Soil transmitted helminth (STH) infections are a group of infections which are acquired by the ingestion of, or contact with, soil containing infectious worm eggs or larvae [18]. STHs have been reported as the most common parasitic infections encountered in humans with an estimation of more than 1 billion people infected with at least one or more helminth parasites. They constitute an important global health challenge in resource deprived parts of the world and are prevalent in areas of poor sanitary conditions [19].
The main species of clinical importance are the intestinal roundworm (Ascaris lumbricoides), the whipworm (Trichuris trichiura) and the hookworms (Necator americanus and Ancylostoma duodenale) [18]. Common symptoms of intestinal helminthiasis include abdominal pains, nausea, itching and diarrhea and in severe cases, anemia, pneumonia, eosinophilia and malnutrition. School-aged children and preschool children are the most vulnerable group who harbor the greatest numbers of intestinal worms. As a result, they experience growth stunting and diminished physical fitness as well as impaired memory and cognition [20]. Although helminth infections are not known to be lethal as compared to other infections, they are recurrent among poor people and pose an enormous impact on the socio-economic status of the society affected [21].
Anthelmintics are a group of antiparasitic drugs that expel worms and other internal parasites out of the body by either stunting or killing them. For the treatment of STHs, the benzimidazoles specifically albendazole and mebendazole are the current treatment drugs of choice [19]. The main challenge with these anthelminthics is the development of resistance due to the intensive use of drugs in both human and live-stock [22]. With few new drugs evolving against helminth infections over the years, the fight against these parasites could become a losing battle, thus the need to search for new alternatives.
1.2 Schistosomiasis—the disease burden and current chemotherapy
Schistosomiasis, widely known as bilharzia, is caused by infection with blood flukes of the genus Schistosoma which is transmitted through contact with infected fresh-water snail vectors. Schistosomiasis is reported to be the 2nd leading endemic parasitic disease in the world after malaria. The disease affects more than 240 million people in tropical and subtropical areas with about 90% cases reported from sub Saharan Africa [23, 24].
Five species of the schistosome parasite namely: Schistosoma mansoni, Schistosoma haematobium, Schisosoma japonicum, Schistosoma mekongi, and Schistosoma intercalatum usually affect humans [25]. In sub-Saharan Africa the main burden of disease is usually attributed to S. mansoni and S. haematobium which cause intestinal and urinary schistosomiasis respectively [10]. The infection is mainly characterized by painful bloody urination in urinary schistosomiasis or blood stained diarrhea in intestinal schistosomiasis. Long term effects include liver fibrosis, renal failure, cancer of the bladder, infertility and increased risk of contracting HIV. In children, schistosomiasis results in malnutrition, growth retardation, cognitive defects and chronic anemia [6, 26].
For the eradication of schistosomiasis, control programmes have been based on preventive chemotherapy. The WHO endorsed and advocated for mass drug administration (MDA) especially among school children utilizing a single oral dose of 40 mg/kg praziquantel [27]. Unfortunately, the unavailability of the drugs due to cost, poor drug coverage, inequity of access to chemotherapy and non-compliance to therapy due to adverse side effects have impeded the progress of this approach [7, 28]. The expansion of preventive chemotherapy has also raised concerns about the potential development of resistance to praziquantel (PZQ) which remains the only commercially readily available drug for the control of schistosomiasis [29]. Some studies have reported low cure rates of PZQ attributing this to possible mutation of the schistosome parasite as well as inactivity of PZQ against early stages of the worms [30, 31]. It is thus not a satisfactory situation to have only one single effective treatment. Ideally, other anti-schistosome drugs should be developed so that the classical strategy of avoiding development of resistance could be followed.
1.3 Methods used in this review for identifying medicinal plants with anthelminthic and anti-schistosomal activities
Reported anthelmintic and anti-schistosomal activities of medicinal plants collected from various parts of Ghana were obtained from electronic databases including PubMed, SciFinder and Google Scholar. The inclusion criteria were that: (i) plants should be used in Ghanaian traditional medicine for treatment of worm infestations or expulsion of worms and schistosomiasis (urinary and intestinal) or other condition characterized by the symptoms of the above diseases (ii) plant should have been investigated for anthelmintic or anti-schistosomal (cercarididal) activity using one or more validated in vitro or in vivo models (iii) the right botanical names, plant parts used, types of extracts prepared, active constituents and mechanisms of action if investigated were mentioned. Consideration was also given to plants with significant activity differences with reference to control groups.
2. Plants with anthelminthic activity identified from Ghana
The anthelmintic activity of plant extracts was mostly studied by evaluating their effect on worms after direct exposure for a period of time. Earthworms including Pheretima posthuma, Lumbricus terrestris, Eudrilus eugeniae and Caenorhabditis elegans were employed as target organisms due to their anatomical and physiological similarity to the human intestinal round worm, ease of availability, adaptability to laboratory conditions and ease of handling.
Alchornea cordifolia, commonly called the Christmas bush is a straggling, laxly branched evergreen dioecious shrub growing up to about 8 m tall. It is locally known as ‘agyama’ in the Ghanaian Akan language and an essential medicinal plant in traditional medicine. Various parts of the plant are used to treat jaundice, diarrhea, rheumatic pains, malaria, fever, wounds, colds, asthma, amoebic dysentery and worm infections. Other literatures report its use in the treatment of urinary and gastrointestinal infections, leprosy, yaws, filariasis as an antidote to snake venom [32].
The anthelminthic potency of the petroleum ether, chloroform and methanol extracts of A. cordifolia leaves were investigated by evaluating its effect on the gross motility and mortality of earthworms (Pheretima posthuma). The extracts displayed significant (p < 0.001) concentration-dependent anthelminthic activity at concentration range of 0.75 to 12.00 mg/mL. At the highest concentration, worm paralysis was effectuated between 10 and 26 mins whiles death occurred between 57 to 93 min. The effect of the extracts in reducing the paralysis and death times of the worms was significantly higher than the effect on albendazole-treated worms [33].
2.2 Alstonei boonei De Wild (Apocynaceae)
Alstonia boonei is an indigenous African tree mostly distributed in the evergreen rain forest of tropical West Africa. In Ghana it is locally called ‘Nyame dua’ meaning God’s tree in the Akan language. In the western coastal regions of Africa, this plant is well known for its extensive use in traditional medicine for treating rheumatism, general body pains, worm infestation and diabetes. A cold infusion of the fresh or dried bark is used as a vermifuge to expel intestinal worms and other intestinal parasites in children [34].
The methanol extracts (50–150 mg/mL) of the stem bark and roots of A. boonei were investigated in vitro for anthelmintic effects against the adult Indian earthworm, Pheretima posthuma by direct exposure of worms to the extracts. The stem bark extract exhibited a concentration dependent anthelmintic activity causing paralysis of worms within 15–55 mins and death within approximately 100 mins which was significant (p < 0.01) compared to the untreated group. The stem bark extract had a better anthelmintic effect than the root bark [35].
In another study, the aqueous and ethanolic stem bark extracts (50–200 mg/mL) of A. boonei demonstrated significant anthelmintic activity against Lubricus terretris. While worms in the untreated group saw no paralysis or death after 120 mins of exposure, the extract-treated worms were paralyzed within 8–16 minutes of exposure and died within approximately 21–27 minutes of exposure [36].
2.3 Azadirachta indica A. Juss. (Meliaceae)
Azadirachta indica, commonly known as neem, is a fast-growing and long lived evergreen tree which grows up to about 15 m tall with long, spreading branches that form a dense, large rounded crown. The plant is a multipurpose medicinal plant which also provides food and timber and is widely distributed in several regions of Asia and Africa. It is well known for its insecticidal and insect-repelling property. Various parts of the plants are reported to be used for the treatment of many ailments in traditional medicine including malaria, fever, upper respiratory tract infections, wound healing, sexually transmitted infections and skin diseases [37].
The anthelmintic activity of the ethanolic extract of A. indica seeds was investigated in vivo using albino rats (Rattus norvegicus) infected with helminth species including: Hymenolepsis diminuta, Enterbius vermicularis and hookworm. The rats were treated with the alcoholic extracts (20–60%) over a 3-week period and fecal samples were examined for eggs. The extract treated groups showed declining levels of egg count by the 3rd week and complete elimination of worms by the end of 21 days when treated with 40–60% of neem seed extract. Weight loss and death were however recorded at 60% concentration of extract raising some concern about the toxicity of the seed extract [38].
2.4 Carica papaya Linn. (Caricaceae)
The pawpaw tree is well known for its nutritional and medicinal values. The leaf decoction is used as a galactogogue and in the treatment of tonsillitis, ulcerative stomatitis, hemorrhoids, asthma, urinary tract infections, as poultice for sores and gingivitis and in the treatment of helminth infections. The roots are used as antidote to various poisons. The fruits are used to treat indigestion, chronic diarrhea, ringworm infections, bleeding piles, and amoebic dysentery [39]. Almost all parts of the plant are documented to be used for managing helminth infections. In Ghana, 74% traditional healers used this plant for treating helminth infections [40].
In a comparative assessment of the anthelminthic activity of various parts of the plant, the hydroethanolic extracts of the leaves, stem bark, and seeds of Carica papaya were tested against P. posthuma as the target organism. The results indicated that all crude extracts prepared were more effective than albendazole in reducing paralysis (p < 0.0001) and death times (p < 0.0001) of worms. Extracts from the seeds at 2.5 mg/mL were the most effective causing worm paralysis and death at 9.26 ± 0.03 and 20.12 ± 0.01 mins respectively. This was more potent than the standard anthelmintic albendazole at the same concentration which gave paralysis and death times of 19.45 ± 0.57 and 31.43 ± 0.28 mins respectively [41].
Ethnopharmacological reports from parts of Ghana revealed the extensive use of the leaves of Combretum mucronatum for treatment of human and livestock helminth infection [40]. The leaves from this plant species is monographed in the Ghana Herbal Pharmacopeia for the treatment of infections with worms [42].
In a previous study, the alcoholic leaf extract of C. mucronatum was assayed in vitro for anthelmintic activity against free-living nematode, Caenorhabditis elegansusing levamisole as a positive control. The extract demonstrated anthelmintic activity with a worm survival rate of 89.2% at 0.1 mg/mL and 58.1% at 1 mg/mL [40].
In another study, fractions and purified compounds from C. mucronatum leaves were tested in vitro for their anthelmintic activity against C. elegans. Unsubstituted oligomeric proanthocyanidins (PACs) mainly composed of epicatechin units were identified as the active compounds of the hydroethanolic leaf extracts. The compounds demonstrated a dose-dependent anthelmintic activity ranging from 1 to 1000 mM and activity was found to increase with increasing molecular size. The anthelmintic activity was suggested to be by interaction of the PACs with some unidentified proteins of the target organism [43]. Further, the mechanism of anthelmintic activity of the PACs was determined by transcriptome analysis. PACs were found to interact with proteins within the worm’s intestinal membrane as well as enzymes and peptides to elicit anthelmintic effects [44]. Another proposed mechanism was interaction of the tannins with cuticular proteins, particularly proline-rich collagen in the worm cuticle [45].
2.6 Cyperus difformis Linn. (Cyperaceae)
Cyperus difformis is an annual plant with smooth leaves and fibrous reddish roots. It is native to the subtropical and tropical areas but also distributed and widespread in South Europe, Asia and Americas. It is regarded as one of the world’s commonest weeds found growing in wet swampy soils among rice plantation. It is very common in Ghana and traditionally used for the management of scorpion bites and malaria [46].
The anthelmintic and helminth resistance modifying activities of methanol extract of C. difformis was investigated against the adult Indian worm, P. posthuma using albendazole, mebendazole and levamisole as reference anthelmintics. The extract exhibited a concentration dependent anthelmintic activity against P. posthuma with significant (p < 0.001) paralysis and death times of 66.67 ± 1.8 and 140.7 ± 2.3 mins respectively at extract concentration of 20 mg/mL [47].
Further the extract at 1, 2 and 5 mg/mL significantly potentiated the activity of albendazole, mebendazole and levamisole against the test organism. In the presence of 2 mg/mL of the extract the paralysis and death times of albendazole (8 mg/mL) against P. posthuma were reduced from 41.33 ± 0.33 and 106.67 ± 0.88 min respectively to 33.33 ± 0.88 and 85.67 ± 1.2 min, respectively. Similar results were obtained for mebendazole and levamisole [47].
2.7 Garcinia cola Heckel (Guttiferae)
Garcinia cola also known as “bitter cola” is a valuable medicinal plant in African traditional medicine widely accepted for its numerous medicinal properties. It is usually called the wonder plant due to the usefulness of every part of the plant. The seeds are chewed as an aphrodisiac and used to cure cough, dysentery and upper respiratory tract infections [48, 49]. The latex from the stem is used against sexually transmitted infections and applied externally to heal wounds. The sap is used in curing parasitic diseases. Chewing sticks produced from the stems are used as masticatory for nervous alertness and for treating coughs and throat infections [50].
In a previous study, the methanol stem bark extract of G. cola (1—50 mg/mL) demonstrated a concentration dependent anthelmintic activity, decreasing paralytic and death times of P. posthuma with increasing extract concentrations. At 50 mg/mL, the extract had a paralytic time of 39.29 ± 0.12 min and death time of 54.29 ± 0.01 [51].
2.8 Morinda lucida Benth. (Rubiaceae)
Morinda lucida is an evergreen shrub growing from about 3 m to 18 m tall. It has a dense crown with slim, crooked branches. The plant is occasionally grown in home gardens. It is locally called ‘konkroma’ in the Ghanaian Akan language. It is a multipurpose species yielding dyes, timber, fuel and traditional medicines. The plant is reported to be used in managing diabetes, hypertension, dysentery, stomach-ache, leprosy and gonorrhea. Traditionally, the stems are used to treat piles while the leaves are used to treat fever. A decoction of the bark or leaf is used in the treatment of jaundice and against itch and ringworm. The leaves and twigs are sold as a medicinal tonic for young children [52].
In a previous study, the methanol stem bark extract of M. lucida (10–50 mg/mL) reduced worm motility and caused death of the adult Indian earth worm, P. posthuma with a paralytic time of 18.17 ± 0.03 min and death time of 24.34 ± 0.21 min at 50 mg/mL [51].
2.9 Moringa oleifera Lam. (Moringaceae)
Moringa oleifera is a fast growing perennial evergreen or deciduous plant which grows up to a maximum height of 7–12 m. It has an open crown of drooping fragile branches bearing feathery foliage of opposite pinnate leaves, a crooked bole and dark gray stem bark. M. oleifera has been naturalized in many tropical and subtropical regions of the world including Africa, Arabia, South Asia, South America and India where it is commonly referred to as horseradish tree and drumstick tree [53]. Various parts of the plant are used in traditional medicine to treat various diseases including skin infections, anemia, asthma, bronchitis, catarrh, chest congestion, cholera, diabetes, hypertension and many other illnesses [54].
The foliage of M. oleifera was investigated for anthelmintic activity in wild caught Achatina achatina Linnaeus (edible snails). After feeding the snails on the foliage for 10 weeks, the proportion of parasitic infection in the treated group was estimated using dissecting and microscopic techniques. At the end of the treatment period, 96% of snails in the untreated group were observed to have their kidneys infected with roundworms as opposed to 24% of snails in the treated group. The percentage prevalence of parasitic infection in the treated and control groups was significantly different (p < 0.0001). Similar results were recorded for the infection of the lungs highlighting the anthelmintic value of M. oleifera in the control of worm infection in edible snails [55].
2.10 Ocimum basilicum Linn (Lamiaceae)
Ocimum basilicum is a tender-growing aromatic annual herb indigenous to West Africa and India. It is commonly called basil or sweet basil and locally known in the Ghanaian Akan language as ‘Nunum’. The herb is ubiquitously known for its therapeutic potentials in African folk medicine. In Ghana, basil is used in its fresh form as spice and flavoring in soups and sauces due to its strong spicy aroma. The whole plant is used to treat worm infestation, inflammation, pain, diarrhea, gastrointestinal infections and eye-related diseases [56].
In vitro anthelmintic activity of the hexane and ethanolic extracts of the fruits of O. basilicum was investigated against Eudrilus eugeniae. At a concentration range of 0.25–5 mg/mL, the extracts displayed a concentration dependent anthelmintic activity which was observed to be significantly (p < 0.001) higher compared to mebendazole-treated worms. At 5 mg/mL, paralysis was observed at 11.85 ± 0.71, 27.90 ± 0.42 and 94.04 ± 2.57 mins for the ethanol extract, hexane extracts and mebendazole-treat worms respectively. Similarly, death of worms was recorded at 24.74 ± 0.42, 85.18 ± 0.07 and 522.77 ± 1.53 mins respectively for the ethanol extract, hexane extracts and mebendazole [57].
2.11 Paullinia pinnata L. (Euphorbiaceaae)
Paullinia pinnata is a woody climber growing in tropical regions worldwide. In Ghana, it is locally called ‘toantini’ in the Akan language. Preparations from the whole plant is used to treat dysentery. The mashed roots are used as poultice to heal chronic wounds and to treat leprosy. The root decoction is also used to cure coughs, pneumonia, gonorrhea, fractures, bacterial infections and abscesses. It is popularly known for its aphrodisiac property and used to treat erectyle dysfunction [58]. In addition, extracts of leaves and roots have been described for the treatment of helminth infestations particularly ancylostomiasis [40].
The hydroethanolic extract of the roots of P. pinnata was investigated in an in vitro mortality assay against the free-living nematode Caenorhabditis elegans as well as the larval stages of the parasitic helminths: Ancylostoma caninum, Haemonchus contortus, Toxocara cati and Trichuris vulpis. From the assay, the extract showed lethal activity against T. cati (LC50 = 112 μg/mL), T. vulpis (LC50 = 17 μg/mL), and C. elegans (LC50 = 2.5 of mg/mL), but not against A. caninum. Additionally, the effects of the extract on egg hatching and larval migration of the sheep parasite, Haemonchus contortus were investigated in vitro, but no inhibitory activity was observed [59].
In another study, the 70% aqueous acetone extract, solvent fractions and isolated compounds from the roots of P. pinnata were investigated for anthelmintic against C. elegans. From the results, the ethyl acetate fraction showed the highest anthelmintic effects with an LC50 of 1.1 mg/mL followed by the crude extract (LC50 = 1.9 mg/mL) and the aqueous fraction (LC50 = 2.9 mg/mL). Oligomeric proanthocyanidins were identified as the main active compounds. A mortality rate of at least 70% was observed for all proanthocyanidin containing fractions at 1 mg/mL [60].
2.12 Plumbago zeylanica Linn. (Plumbaginaceae)
Plumbago zeylanica is a perennial shrub with semi woody stems and numerous branches. It is a valuable medicinal plant widely used in Africa and Asia for the treatments of common ailments like hemorrhoids, diarrhea, leprosy, arthritic pains, toothache and as aphrodisiac and wound healing [61].
In a previous, observations were made for the time taken for different solvent extracts of the leaves of P. zeylanicum at concentrations of 300, 100 and 30 mg/mL to paralyze and kill Pheretima posthuma. The ethyl acetate extracts showed significant (p < 0.0001) concentration-dependent anthelminthic activity with the highest effect at 300 mg/mL causing paralysis at 7.39 ± 0.94 min and death at 11.81 ± 1.10 min. The methanol extract at 300 mg/mL demonstrated slightly lower anthelmintic effect with paralysis at 17.23 ± 1.68 min and death at 21.83 ± 2.60 min [62].
2.13 Rauwolfia vomitoria Afzel. (Apocynaceae)
Rauwolfia vomitoria commonly called the African Snakeroot or African Serpent root is a small tree or shrub that grows up to about 20 m tall in tropical Africa. It is locally called ‘kakapenpen’ in the Asante dialect of Ghana. In traditional medicine, the plant is recorded to be used in the treatment of convulsions, malaria fever, insomnia, arthritis, pain, high blood pressure, diabetes, stomach problems and as an emetic. The leaves are applied topically for skin infections, swelling and snake bites. It is placed in the rectum for the expulsion of worms and for dysmenorrhea [46].
The leaves and stem bark of R. vomitoria demonstrated significant (p < 0.001) anthelmintic activity against the Indian adult earthworm P. posthuma. The methanol extracts of the stem bark caused paralysis of worms at 11.17 ± 0.088 min and reduced the death time to 21.67 ± 0.733 similar to the effect of albendazole at 10 mg/mL which had a worm death time of 21.03 ± 0.258 min [63].
Sclerocarya birrea is a dioecious small to medium sized tree growing up to about 20 m high and 1.2 m in diameter. The plant is distributed from Gambia, Ghana and Nigeria in West Africa, across Cameroon in Central Africa, to Ethiopia and Sudan in East Africa and to South Africa, usually found growing in open farm lands and natural vegetation [64]. The stem-bark, roots and leaves are used to treat several ailments including diabetes mellitus, diarrhea, dysentery, proctitis, ulcers, inflammation, arthritis, hypertension, skin diseases, and malaria [65].
The anthelmintic activity of the aqueous and ethanolic extracts of the roots of S. birrea were evaluated against earth worms. The extracts displayed significant (p < 0.001) concentration-dependent anthelmintic activity at 12.00 to 0.1875 mg/mL. The observed effect was higher compared to albendazole-treated worms [66].
2.15 Vernonia amygdalina Del. (Asteraceae)
Vernonia amygdalina is tropical shrub which grows up to about 3 m high. The plant is distributed throughout tropical Africa and has been domesticated in some parts of West Africa including Nigeria and Ghana where it is commonly called the bitter leaf. It is a highly valuable vegetable in West and Central Africa which is consumed as part of various dishes. In traditional medicine the leaf decoction is used to treat fever, malaria, diarrhea, dysentery, hepatitis and cough, as a laxative and as a fertility inducer [67]. The root extracts are also used for treating malaria and gastrointestinal disorders. One of the most common medicinal uses of V. amygdalina is as a treatment against intestinal worms including nematode infections [68]. The use of the leave decoctions against intestinal worms, especially pinworms was confirmed in an ethnobotanical survey in the Ashanti Region of Ghana [40].
In a previous study, the anthelmintic activity of V. amygdalina leaves were investigated against Lumbricus terrestris (earth worm). Unlike the negative control groups which remained alive and active after 6 hours of exposure to normal saline, all worms treated with the aqueous and ethanol leaf extracts (50–200 mg/mL) of V. amygdalina were noted to be paralyzed within 4.05 ± 1.06 to 59.94 ± 8.25 and 3.56 ± 0.37 to 33.18 ± 12.4 mins respectively (p < 0.0001). The effect was concentration dependent [36].
In another study, the stem bark extracts (ethanol and chloroform extracts) of V. amygdalina were observed to produce a synergistic anthelmintic effect when combined with the seeds of Carica papaya [69].
2.16 Voacanga Africana Stapf. (Apocynaceae)
Voacanga africana is a small tree or shrub, reaching up to 6 m tall in height with a low widely spreading crown. In Ghana, it is locally known as ‘ofruma’ in the Asante language. Various plant parts are used medicinally throughout its distribution area [70]. The leaf decoction is used to treat dysentery, diarrhea, cutaneous and sub-cutaneous parasitic infections, leprosy, oedema, gout, paralysis and convulsion. The stem bark or roots decoctions are used as wound healing agents and used to treat boils, malaria, sexually transmitted diseases like gonorrhea, and skin diseases such as eczema and scabies. They are also taken to treat cardiovascular diseases and rheumatoid arthritis. The leaf latex is put in the teeth to treat dental caries or dripped in the eye to cure ophthalmia [46].
The methanol extracts of the leaves and stem bark V. africana were evaluated for in vitro anthelmintic activity by determining the effects of the extracts on the paralytic and death time of P. posthuma using albendazole as reference. The bark extract (20–50 mg/mL) demonstrated a significant (p < 0.001) concentration dependent anthelmintic effect by decreasing the paralysis and death times of worms. At 50 mg/mL, the stem bark extract caused worm paralysis within 7.03 ± 0.491 min and death at 14.77 ± 0.117 min [63].
2.17 Xylopia aethiopica (Dunal) A. Rich. (Apocynaceae)
Xylopia aethiopica is popularly known as the African pepper and locally called ‘Hwentia’ in the Ghanaian Akan language meaning slender nose, referring to the shape of the fruit. X. aethiopica is known for its numerous medicinal properties in African traditional medicine. The bark infusion is used in the treatment of asthma, stomach aches and rheumatism. The bark powder is also applied topically on ulcerous wounds and used locally for the treatment of cancer and stomach ulcers. The root powder is known to relief toothache and pyorrhea [71].
The ethanolic extract of the dried fruits and leaves (300–300 mg/mL) were investigated for anthelmintic activity against earth worms. The anthelmintic activity of the fruit extract was more potent that the leaf extract. Both extracts demonstrated a concentration dependent activity with the fruit extract demonstrating significant paralytic and death times (p < 0.001) at 100 and 300 mg/mL [72].
3. Plants with cercaricidal and anti-schistosomal activities identified from Ghana
Anthelmintic activity against Pheretima posthuma [33]
Alstonia boonei
Apocynaceae
Alstonia
Roots, stem bark
Anthelmintic activity against Pheretima posthuma, Lubricus terretris [35, 36]
Azadirachta indica
Meliaceae
Neem
Seeds Leaves
Anthelmintic activity against Hymenolepsis diminuta, Enterbius vermicularis and hookworm [38] Cercaricidal and adulticidal activity against Schistosoma mansoni [73]
Carica papaya
Caricaceae
Pawpaw
Leaves, stem bark, seeds
Anthelmintic activity against Pheretima posthuma [41]
Combretum mucronatum
Combretaceae
—
Leaves
Anthelmintic activity against Caenorhabditis elegans [40, 43, 45]
Cyperus difformis
Cyperaceae
—
Whole plant
Anthelmintic activity against Pheretima posthuma [47]
Dichapetalum crassifolium
Dichapeltaceae
—
Stems, roots
Anti-schistosomal activity against eggs obtained from clinical isolates of Schistosoma haematobium [75]
Erythrophloem ivorense
Euphorbiaceae
—
Leaves, stem bark Roots
Cercaricidal activity against post-infective larvae (schistosomule) and adult parasite of Schistosoma mansoni [77] Cercaricidal activity against freshly shed cercariae from Schistosoma haematobium [78]
Garcinia cola
Gutifferae
Bitter kola
Stem bark
Anthelmintic activity against Pheretima posthuma [51]
Holarrhena floribunda
Apocynaceae
—
Stem bark
Cercariae from Schistosoma haematobium
Morinda lucida
Rubiaceae
—
Stem bark
Anthelmintic activity against Pheretima posthuma [51] Cercaricidal activity against Schistosoma mansoni cercariae Adulticidal effect against S. mansoni adult worms [73]
Moringa oleifera
Moringaceae
Moringa
Foliage
Anthelmintic activity against round worms in wild edible snails (Achatina achatina) [55]
Nauclea latifolia
Rubiaceae
African peach
Stem bark
Cercaricidal activity against Schistosoma mansoni cercariae Adulticidal effect against S. mansoni adult worms [73]
Ocimum basilicum
Lamiaceae
Basil
Fruits
Anthelmintic activity against Eudrilus eugeniae [57]
Paullinia pinnata
Euphorbiaceae
—
Roots
Anthelmintic activity against the free-living nematode Caenorhabditis elegans and larval stages of the parasitic helminths: Ancylostoma caninum, Haemonchus contortus, Toxocara cati and Trichuris vulpis [60]
Plumbago zeylanica
Plumbaginaceae
—
Leaves
Anthelmintic activity against Pheretima posthuma [62]
Phyllanthus amarus
Euphorbiaceae
—
Leaves
Cercaricidal activity against Schistosoma mansoni cercariae
Rauwolfia vomitoria
Apocynaceae
Snakeroot
Leaves, roots Roots, stem bark
Anthelmintic activity against Pheretima posthuma [63] Cercaricidal activity against Schistosoma mansoni cercariae Adulticidal effect against S. mansoni adult worms [73]
Sclerocarya birrea
Anacardiaceae
Roots
Anthelmintic activity against Lumbricus terrestris [66]
Vernonia amygdalina
Asteraceae
Bitter leaf
Leaves, stem bark Leaves
Anthelmintic activity against Lumbricus terrestris [36] Cercaricidal activity against Schistosoma mansoni cercariae Adulticidal effect against S. mansoni adult worms [73]
Voacanga africana
Apocynaceae
—
Leaf, stem bark
Anthelmintic activity against Pheretima posthuma [63]
Xylopia aethiopica
Apocynaceae
African black pepper
Fruits, leaves
Anthelmintic activity against Lumbricus terrestris [72]
Table 1.
Medicinal plants from Ghana with anthelmintic and anti-schistosomal activity.
3.1 Azadirachta indica A. Juss (Meliaceae)
[Refer to Section 2.3 for plant description].
The methanol leaf extract of A. indica was investigated for cercaricidal activity against freshly shed cercariae of Schistosoma mansoni. At a concentration range of 31.2–1000 μg/mL, the leaf extract caused a steady increase in the number of dead cercariae during an observation period of 15 to 180 mins. At 60 mins, 250 μg/mL of extract was found to cause 100% mortality of cercariae. At the end of the observation period (180 mins) the leaf extract recorded an IC50 of 27.62 μg/mL which was about four times lower than the effect of the positive control Balanites aegyptiaca (IC50 of 5.95 μg/mL) [73].
The effect of A. indica leaf extract on the viability of adult schistosome worms (i.e. adulticidal effect) was further investigated. At the end of 120 h, the extract at 62.5–1000 μg/mL was found to be lethal to the incopula adult worms. Further in an in vivo study, the ability of the leaf extract (500 mg/kg p.o.) to reduce the worm recovery and worm burden in S. mansoni infected mice was investigated. After a two-week period of treatment, the mean number of worms recovered from A. indica-treated mice was 19.80 ± 8.194 which was significantly lesser than that of the untreated mice (40.20 ± 3.072) [73].
The effect of the extract on the weight of spleen and liver of infected mice were all significantly lesser in the A. indica-treated group than that of the untreated group (p < 0.05). Organ histology also revealed only few granulomas which were smaller in diameter in the treatment groups whereas those in the untreated were severe (p < 0.05). Treated cercariae-infected mice group also had relatively less severe inflammatory cell infiltration compared with untreated group [73].
Dichapetalum crassifolium is a scandent shrub, about 1.5 m tall usually found growing in the rain forest, shady places, primitive woods and rocky areas of African countries including Ghana, Angola, Benin, Cameroon, Ivory Coast, Liberia, Nigeria, Sierra Leone, Tanzania, Togo and Zambia [74].
Crude extracts (pet-ether, ethyl acetate and methanol) and isolated triterpenoids from the stems and roots of D. crassifolium were investigated for anti-schistosomal activity against eggs obtained from clinical isolates of Schistosoma haematobium using the 96-well plate-egg hatch assay [75].
For the stem extracts, the ovicidal potency was in the following order petroleum ether (IC50 = 443.70) > EtOAc (IC50 = 638.00) > MeOH (IC50 = 893.70 μg/mL). The IC50 values for the root extracts were 248.60, 546.40, and 566.30 μg/mL respectively for the EtOAc, pet-ether and MeOH extracts.
The isolated compounds (Friedelan-3-one, β-Sitosterol/stigmasterol, Dichapetalin M and Dichapetalin A) showed higher ovicidal activity than the extracts though activities for both extracts and compounds were lower compared to the standard drug, praziquantel. The highest ovicidal potency was exhibited by β-sitosterol/stigmasterol mixture with an IC50 of 177.90 μg/mL which was about 11 times less potent than praziquantel (15.47 ± 0.06 μg/mL). The next highest was dichapetalin A (151.10 μg/mL) whiles friedelan-3-one showed the least potency with IC50 of 378.10 μg/mL. From the root extract, Dichapetalin M showed ovicidal effect with IC50 of 191.00 μg/mL [75].
3.3 Erythrophleum ivorense Afzel (Euphorbiaceae)
E. ivorense is a large tree which grows to about 40 m tall, with a cylindrical bole, sometimes fluted at the base. It is widely distributed in the evergreen primary and secondary forests of tropical Africa where it is commonly called by names like ‘forest ordeal tree’, ‘red water tree’ and ‘sasswood tree’. Among the Akan tribe in Ghana, it is known as ‘potrodum’. The stem-bark and roots are usually employed in the treatment of epilepsy, emesis, pain, oedema, constipation and worm infestations [76].
The cercaricidal activity of the leaf and stem bark extracts of E. ivorense was investigated against two developmental stages of Schistosoma mansoni namely: the post-infective larvae (schistosomule) and the adult parasite. Various solvent fractions were assayed against the schitosomules at a concentration range of 0.31–100 μg/mL and against adult parasites at 1.25 mg/mL. The acetone fractions of both leaf and bark demonstrated the highest anti-schistosomal activity causing severe phenotypic alterations (immobility/inactivity, change in shape, translucence, surface disintegration) and death of schistosomules at all dilutions (except 0.31 𝜇g/mL) at 24 h and 48 h. For adult parasites, severe phenotypic changes specifically damage to the adult parasite’s tegument (surface) was observed for the acetone fraction of the stem bark extract. The adult worms were observed to be uncoordinated by 5 h, darkened in color by 24 h and died at 48 h exhibiting tegumental damage [77].
In another study, the in vitro cercaricidal activity of solvent fractions and isolated compounds from the root bark of E. ivorense was investigated against freshly shed cercariae from Schistosoma haematobium. Whereas the cercariae showed normal viability without any morphological changes (tail loss) throughout the entire duration of the experiment in the untreated group, exposure of cercariae to the crude hydro-ethanolic extract, its fractions and compounds caused a concentration and time-dependent decrease in viability of cercariae. Within two hours of incubation, all cercariae died at the various concentrations of test compounds and extracts. Eriodictyol, was the most potent compound with an IC50 of 1.23 ± 0.05 μg/mL. All test samples exhibited a much higher cercaricidal activity than the standard drug praziquantel which caused only 40% mortality of cercariae at the highest concentration tested (IC50 = 695.50 ± 0.05 μg/mL) [78].
3.4 Holarrhena floribunda (G. Don) Dur. & Schinz. (Apocynaceae)
Holarrhena floribunda is native to West Africa and is known in Ghana as ‘osese’ among the Akans. The plant is traditionally used in the treatment of malaria, fever and bareness in females. It has antifungal, antibacterial and antidiabetic properties [79, 80].
The hydroethanolic and alkaloidal extracts from the stem bark of H. floribunda were tested on cercariae from Schistosoma haematobium at concentrations between 15.625 and 500.00 μg/mL. After 180 mins of contact with test samples, the ethanolic extract exhibited the highest cercaricidal potency with an IC50 of 20.09 ± 1.11 μg/mL higher than the effect of paraziquantel (IC50 = 695.50 ± 1.12). The alkaloidal extract also exhibited cercaricidal potency with an IC50 of 53.20 ± 1.33 μg/mL. The isolated compounds: holonamine, holadienine and conessine exhibited cercaricidal potency with IC50 values of 53.24 ± 1.28, 470.80 ± 1.00 and 33.28 ± 1.04 respectively. The results confirmed the activity of Holarrhena floribunda against S. heamatobium ceracriae [81].
3.5 Morinda lucida Benth (Rubiaceae)
[Refer to Section 2.8 for plant description].
In a previous study, the cercaricidal activity of the methanol stem bark extract of M. lucida was carried out. The extract at a concentration of 500 μg/mL elicited 100% mortality of S. mansoni cercariae within 120 mins of exposure giving an IC50 value of 262.3 μg/mL, which was however lower than the effect of the positive control Balanites aegyptiaca (IC50 of 5.95 μg/mL). Further, the in vitro adulticidal effect of the stem bark extract on adult schistosome worms revealed that at a concentration of 125–1000 μg/mL, the extract was found to be lethal to the adult worms within 120 h of exposure [73].
3.6 Nauclea latifolia Carl Lin. (Rubiaceae)
Nauclea latifolia, commonly called the African peach, is a deciduous shrub with an open canopy distributed throughout tropical and savanna regions of Africa and Asia. It varies widely in height from around 10–30 m according to soil and moisture conditions. The plant is used against various medical conditions such as diabetes, fever, indigestion and cough [82].
Previous studies on the cercaricidal activity the methanolic extract of stem bark of N. latifolia revealed 100% mortality of S. mansoni cercariae at a concentration of 250 μg/mL at 120 min (IC50 = 195.9 μg/mL). Further the extract was found to exhibit schistomicidal effect being lethal to the adult incopula worms at a concentration range of 500–1000 μg/mL within 120 mins of exposure [73].
3.7 Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae)
P. amarus is a small herb bearing ascending herbaceous branches normally found around coastal and muddy areas. The whole plant is used in the treatment of gonorrhea, menorrhagia and other urinary and sexually transmitted infections. It is useful in gastropathy, diarrhea, dysentery, intermittent fevers, ophthalmopathy, scabies, ulcers and wounds [83].
The methanolic extract (250 μg/mL) of P. amarus leaves exhibited moderate cercaricidal activity on freshly shed S. mansoni cercariae causing 100% mortality of cercariae within 180 mins of exposure (IC50 = 250.4 μg/mL). It was further established that at 125–1000 μg/mL, the extract caused a drastic reduction in the viability of adult worms [73].
3.8 Rauwolfia vomitoria Afzel. (Apocynaceae)
[Refer to Section 2.13 for plant description].
The root and stem bark of Rauwolfia vomitoria were evaluated for schistosomicidal effect on two different parasitic stages of Schistosoma mansoni i.e. cercariae and adult worms [84].
The ethanolic extract of the root and stem bark were both found to be active against the cercariae and adult worms. At a concentration range of 62.5–1000 𝜇g/mL the stem bark extract exhibited significant anti-cercarial activity (p < 0.05) with an LC50 of 207.4 and 61.18 𝜇g/mL after 1 and 2 h of exposure respectively. At the highest concentration (1000 𝜇g/mL), there was 100% mortality of cercariae within 90 min of exposure. The roots were less active than the stem bark showing activity at a higher concentration range of 250–1000 𝜇g/mL. The schistomicidal activity of the stem bark and roots were further determined against adult worms. All adult worms exposed to the concentrations range of 250–1000 𝜇g/mL for both plant parts died within 120 h of incubation [84].
3.9 Vernonia amygdalina Del. (Asteraceae)
[Refer to Section 2.15 for plant description].
In a previous study, the evaluation of the cercaricidal and schistosomicidal activities of the methanol extract of the leaves of V. amygdalina revealed significant potency response. At 250 μg/mL, the extract exhibited cercaricidal activity with an IC50 of 35.84 μg/mL within 180 min of exposure. Further, the extract was found to reduce the viability of adult schistosome worms in vitro at 250–1000 μg/mL.
The ability of the leaf extract (500 mg/kg p.o.) to reduce the worm recovery and worm burden in S. mansoni infected mice was further investigated in an in vivo study. After a two-week period of treatment, the mean number of worms recovered from V. amygdalina-treated mice was 12.00 ± 1.549, indicating 48.9%, worm burden which was significantly lower than that of the untreated group (40.20 ± 3.072). While there was significant increase in the weight of the liver and spleen of the untreated infected mice with marked formation of granuloma, V. amygdalina-treat infected mice showed no increase in liver or spleen size and had few granulomas which were smaller in diameter with relatively less severe inflammatory cell infiltration compared [73].
4. Conclusion
The anthelmintic and anti-schistosomal activities of some medicinal plants employed in Ghanaian traditional medicine have been validated. For most of these plants however, the specific bioactive constituents are not yet identified. It is therefore imperative that further studies to isolate and verify the constituents responsible for the observed activities be performed. Further, the evaluation of safety profiles will add substantial value to the reported bioactivities and make these plants attractive for adaptation to pharmaceutical companies for further development.
Conflict of interest
Authors have no conflict of interest to declare.
\n',keywords:"schistosomiasis, worms, parasite, helminth, Ghana, herbal medicine",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/76353.pdf",chapterXML:"https://mts.intechopen.com/source/xml/76353.xml",downloadPdfUrl:"/chapter/pdf-download/76353",previewPdfUrl:"/chapter/pdf-preview/76353",totalDownloads:191,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 24th 2021",dateReviewed:"March 25th 2021",datePrePublished:"April 20th 2021",datePublished:"May 11th 2022",dateFinished:"April 20th 2021",readingETA:"0",abstract:"Parasitic infections including schistosomiasis and soil transmitted helminthiasis are the most commonly encountered Neglected Tropical Diseases (NTDs) in the world. These diseases remain a major public health concern affecting millions of people especially those living in poor regions where access to effective conventional health care is a challenge. Interventions to control these infections in endemic areas have not been successful due to the high cost of drugs, limited availability as well as inequity of access to preventive chemotherapies. Another problem is the development resistance to the limited number of recommended medications due to their intensive use in both human and live-stock. There is an increasing awareness of the potential of natural products as chemotherapeutic agents to combat parasitic infections. Natural products may offer an unlimited source of chemically diverse drug molecules which may be safe, efficient, less toxic, less expensive and readily available for use especially in low-income countries. The Ghanaian flora provides such a ready source for new therapeutic interventions for the local population. Several researches have provided evidence of the anti-parasitic activity of Ghanaian medicinal plants. This chapter provides a review with special focus on medicinal plants collected from Ghana with anthelmintic and anti-schistosomal activity. Evidence of pharmacological activities of crude extracts, fractions and bioactive phytoconstituents as well as possible mechanisms of action where investigated are discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/76353",risUrl:"/chapter/ris/76353",signatures:"Evelyn Asante-Kwatia, Abraham Yeboah Mensah, Lord Gyimah and Arnold Donkor Forkuo",book:{id:"10356",type:"book",title:"Natural Medicinal Plants",subtitle:null,fullTitle:"Natural Medicinal Plants",slug:"natural-medicinal-plants",publishedDate:"May 11th 2022",bookSignature:"Hany A. El-Shemy",coverURL:"https://cdn.intechopen.com/books/images_new/10356.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-276-5",printIsbn:"978-1-83969-275-8",pdfIsbn:"978-1-83969-277-2",isAvailableForWebshopOrdering:!0,editors:[{id:"54719",title:"Prof.",name:"Hany",middleName:null,surname:"El-Shemy",slug:"hany-el-shemy",fullName:"Hany El-Shemy"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"217045",title:"Dr.",name:"Arnold Forkuo",middleName:null,surname:"Donkor",fullName:"Arnold Forkuo Donkor",slug:"arnold-forkuo-donkor",email:"forkuo3@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"303360",title:"Dr.",name:"Evelyn",middleName:null,surname:"Asante-Kwatia",fullName:"Evelyn Asante-Kwatia",slug:"evelyn-asante-kwatia",email:"emireku@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"309974",title:"Prof.",name:"Abraham Yeboah",middleName:null,surname:"Mensah",fullName:"Abraham Yeboah Mensah",slug:"abraham-yeboah-mensah",email:"aymensah@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kwame Nkrumah University of Science and Technology",institutionURL:null,country:{name:"Ghana"}}},{id:"347910",title:"Mr.",name:"Lord",middleName:null,surname:"Gyimah",fullName:"Lord Gyimah",slug:"lord-gyimah",email:"lordgyimah36@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kwame Nkrumah University of Science and Technology",institutionURL:null,country:{name:"Ghana"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Soil transmitted helminthiasis (STH)-the disease burden and current chemotherapy",level:"2"},{id:"sec_2_2",title:"1.2 Schistosomiasis—the disease burden and current chemotherapy",level:"2"},{id:"sec_3_2",title:"1.3 Methods used in this review for identifying medicinal plants with anthelminthic and anti-schistosomal activities",level:"2"},{id:"sec_5",title:"2. Plants with anthelminthic activity identified from Ghana",level:"1"},{id:"sec_5_2",title:"2.1 Alcornea cordifolia (Schumach & Thonn) Müll. Arg. Euphorbiaceae",level:"2"},{id:"sec_6_2",title:"2.2 Alstonei boonei De Wild (Apocynaceae)",level:"2"},{id:"sec_7_2",title:"2.3 Azadirachta indica A. Juss. (Meliaceae)",level:"2"},{id:"sec_8_2",title:"2.4 Carica papaya Linn. (Caricaceae)",level:"2"},{id:"sec_9_2",title:"2.5 Combretum mucronatum Schumach & Thonn. (Combretaceae)",level:"2"},{id:"sec_10_2",title:"2.6 Cyperus difformis Linn. (Cyperaceae)",level:"2"},{id:"sec_11_2",title:"2.7 Garcinia cola Heckel (Guttiferae)",level:"2"},{id:"sec_12_2",title:"2.8 Morinda lucida Benth. (Rubiaceae)",level:"2"},{id:"sec_13_2",title:"2.9 Moringa oleifera Lam. (Moringaceae)",level:"2"},{id:"sec_14_2",title:"2.10 Ocimum basilicum Linn (Lamiaceae)",level:"2"},{id:"sec_15_2",title:"2.11 Paullinia pinnata L. (Euphorbiaceaae)",level:"2"},{id:"sec_16_2",title:"2.12 Plumbago zeylanica Linn. (Plumbaginaceae)",level:"2"},{id:"sec_17_2",title:"2.13 Rauwolfia vomitoria Afzel. (Apocynaceae)",level:"2"},{id:"sec_18_2",title:"2.14 Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae)",level:"2"},{id:"sec_19_2",title:"2.15 Vernonia amygdalina Del. (Asteraceae)",level:"2"},{id:"sec_20_2",title:"2.16 Voacanga Africana Stapf. (Apocynaceae)",level:"2"},{id:"sec_21_2",title:"2.17 Xylopia aethiopica (Dunal) A. Rich. (Apocynaceae)",level:"2"},{id:"sec_23",title:"3. Plants with cercaricidal and anti-schistosomal activities identified from Ghana",level:"1"},{id:"sec_23_2",title:"3.1 Azadirachta indica A. Juss (Meliaceae)",level:"2"},{id:"sec_24_2",title:"3.2 Dichapetalum crassifolium Chodat (Dichapetalaceae)",level:"2"},{id:"sec_25_2",title:"3.3 Erythrophleum ivorense Afzel (Euphorbiaceae)",level:"2"},{id:"sec_26_2",title:"3.4 Holarrhena floribunda (G. Don) Dur. & Schinz. (Apocynaceae)",level:"2"},{id:"sec_27_2",title:"3.5 Morinda lucida Benth (Rubiaceae)",level:"2"},{id:"sec_28_2",title:"3.6 Nauclea latifolia Carl Lin. (Rubiaceae)",level:"2"},{id:"sec_29_2",title:"3.7 Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae)",level:"2"},{id:"sec_30_2",title:"3.8 Rauwolfia vomitoria Afzel. (Apocynaceae)",level:"2"},{id:"sec_31_2",title:"3.9 Vernonia amygdalina Del. (Asteraceae)",level:"2"},{id:"sec_33",title:"4. Conclusion",level:"1"},{id:"sec_37",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Hotez PJ, Kamath A. 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In vitro assessment of anthelmintic activities of Rauwolfia vomitoria (Apocynaceae) stem bark and roots against parasitic stages of Schistosoma mansoni and cytotoxic study. Journal of Parasitology Research. 2017; 2017:1-11'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Evelyn Asante-Kwatia",address:"emireku@yahoo.com",affiliation:'
Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Ghana
Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Ghana
Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Ghana
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Ghana
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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. 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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/441230",hash:"",query:{},params:{id:"441230"},fullPath:"/profiles/441230",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()