Average scores of
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"1610",leadTitle:null,fullTitle:"Analysis of Genetic Variation in Animals",title:"Analysis of Genetic Variation in Animals",subtitle:null,reviewType:"peer-reviewed",abstract:"Analysis of Genetic Variation in Animals includes chapters revealing the magnitude of genetic variation existing in animal populations. The genetic diversity between and within populations displayed by molecular markers receive extensive interest due to the usefulness of this information in breeding and conservation programs. In this concept molecular markers give valuable information. The increasing availability of PCR-based molecular markers allows the detailed analyses and evaluation of genetic diversity in animals and also, the detection of genes influencing economically important traits. The purpose of the book is to provide a glimpse into the dynamic process of genetic variation in animals by presenting the thoughts of scientists who are engaged in the generation of new idea and techniques employed for the assessment of genetic diversity, often from very different perspectives. The book should prove useful to students, researchers, and experts in the area of conservation biology, genetic diversity, and molecular biology.",isbn:null,printIsbn:"978-953-51-0093-5",pdfIsbn:"978-953-51-5214-9",doi:"10.5772/2072",price:139,priceEur:155,priceUsd:179,slug:"analysis-of-genetic-variation-in-animals",numberOfPages:374,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"2dbc70699ec1ca38dc2175c6aeebe710",bookSignature:"Mahmut Caliskan",publishedDate:"February 29th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1610.jpg",numberOfDownloads:50430,numberOfWosCitations:55,numberOfCrossrefCitations:24,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:60,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:139,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2011",dateEndSecondStepPublish:"May 11th 2011",dateEndThirdStepPublish:"September 15th 2011",dateEndFourthStepPublish:"October 15th 2011",dateEndFifthStepPublish:"February 14th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"51528",title:"Prof.",name:"Mahmut",middleName:null,surname:"Çalışkan",slug:"mahmut-caliskan",fullName:"Mahmut Çalışkan",profilePictureURL:"https://mts.intechopen.com/storage/users/51528/images/system/51528.png",biography:"Mahmut Çalışkan is a Professor of Genetics and Molecular Biology in the Department of Biology, Biotechnology Division, Istanbul University, Turkey. He obtained a BSc from Middle East Technical University, Ankara, and a Ph.D. from the University of Leeds, England. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"58931",title:"Genetic Variation of Landraces of Common Bean Varying for Seed Coat Glossiness and Disease Resistance: Valuable Resources for Conservation and Breeding",doi:"10.5772/intechopen.73425",slug:"genetic-variation-of-landraces-of-common-bean-varying-for-seed-coat-glossiness-and-disease-resistanc",body:'The conservation of crop genetic resources is a fundamental step for further breeding of traits of interest. Common bean (
The introduction of common bean to other areas than its natural habitat, such as in Brazil [9], led to new combinations of seed and flower colors, shapes and sizes, growth habits, cycle, photoperiod and yield [10]. It has also shaped the interaction between beans and the environment, leading to new diseases and pests.
In Brazil, common bean is a staple food among most citizens along with rice. Usually, its cultivation is performed in small farming systems along with other crops and animal production systems, providing self-sufficiency for farmers in various regions of the country. Several cycles of selection by local farmers in specific environments have generated new landraces, which are not yet known and available from core collections such as the ones from Centro Internacional de Agricultura Tropical (CIAT, Colombia), United States Department of Agriculture (USDA, USA) and Empresa Nacional de Pesquisa Agropecuária (EMBRAPA, Brazil). Landraces have singular aspects that might assist breeding programs for disease resistance, abiotic stress tolerance, improvement of nutrition facts, among several other desirable aspects of common bean grains.
A particular landrace has been discovered with local farmers from the municipality of Cunha, Sao Paulo state, Southeast Brazil. The farmers referred this landrace as “Serro Azul” and have been cultivating it along with other varieties [11]. Serro Azul shows considerable morphological variability, revealing different types of seeds. It shows high genetic variation for seed colors and patterns [12], disease and insect resistance and nodulation ability [11, 13], which are among the main aspect studies in breeding programs of common bean.
We drive the topic of this chapter highlighting Serro Azul as a case study of how the conservation of landraces might be important for further breeding strategies. First, we describe the importance of landraces of common bean in the discovery of new allele combinations for seed color and pattern genes, using the example of Serro Azul. Then, we briefly discuss the implications of the research of common bean landraces for nutrition and health. Moreover, we outline a significant number of original findings about our landrace in focus, which serve as examples of disease resistance as well as indications of insect resistance. Finally, we guide the reader through other perspectives of the importance of a better knowledge of landraces, their collection and conservation for future endeavors in breeding programs.
Serro Azul is a landrace that was so named by local farmers living in the countryside of the small municipality of Cunha, in São Paulo state, Brazil. From the search along the distinct farms at that area, De Oliveira et al. [11] were able to collect seeds with three main patterns of colors such as gray background with black strips (Serro Azul Malhado—SAM), light brown with glossy seed coat (Serro Azul Brilhante—SAB) and dark gray with dull seed coat (Serro Azul Fosco—SAF). Interestingly, at one of the farms, from a fresh sample of SAF seeds collected (approximately 1 kg), only 10 seeds presented the SAB pattern (Figure 1A shows the phenotypes of SAB and SAF). Seeds with the SAB pattern were crossed to the SAF pattern and the reciprocal as well, and populations were advanced to F4 generation, revealing consistent patterns of segregation for seed glossiness and color [12].
Morphological and anatomical aspects of seeds of the common bean landrace Serro Azul. (A) Parental genotypes (Serro Azul Brilhante—SAB and Serro Azul Fosco—SAF) and the four phenotypes of F2:3 families of the cross SAF × SAB. The parent SAB has a glossy brown seed coat, while the SAF seed coat shows a dull gray phenotype. The F2:3 families segregate for both color and glossiness. (B) Principal component analysis with the L*a*b* variables, obtained with a colorimeter for F2:3 families of the cross SAF × SAB. a*: the amount of green or red; b*: the quantity of blue or yellow; L*: the quantity of brightness. (C) Scanning electron profiles of the seed coat surface (left image) and their transversal profile (central image) and histological sections (image on the right) of transversal sections of the seed coat of both SAB and SAF. PE: palisade epidermis; H: hypodermis; PT: parenchymatous tissue. The scale bars indicate 10 μm (left image), 20 μm (central image) and 100 μm (right image) (adapted from [
Serro Azul has been the object of a few studies, considering its importance to local farmers and the need of improving its productivity. It has been subjected to many diseases, such as anthracnose, and pests. De Oliveira et al. [11] and De Oliveira and Tsai [13] showed low yield from this variety from experiments performed at different farms in Cunha, SP, when no fertilizer was applied. This treatment represented the traditional way that farmers cultivated this landrace at their farms. However, when a sort of fertilizer treatments were applied in soil cultivated with this variety, along with one commercial standard at the time (IAC-Carioca 80SH), the yield was significantly improved from around 930 kg ha−1 (without fertilizer) to 1360 kg ha−1 (fertilizer application along with lime and foliar spray of molybdenum) [13].
The genetic control of seed coat color, pattern and glossiness in common bean has been a major issue for scientists in decades. Frequently, the gene nomenclature for loci related to such traits was confusing, leading to a series of meetings for establishing standard nomenclatures (Bean Improvement Cooperative meetings). As regards seed glossiness, Bassett [14] has clarified the differences between glossy and opaque seed coats through a series of genetic crosses, providing genetic stocks (pure lines for specific alleles of seed coat loci) that have been used since then for unraveling the genetic and biochemical aspects of the trait.
Landraces might be the source of additional alleles or allele combinations for studying genes related to color, pattern and glossiness of the seed coat. Moreover, these new sources might be interesting for being added to the breeding programs concerned with such traits. The study of Konzen and Tsai [12] examined the particular aspect of Serro Azul of segregating for seed glossiness and color patterning. The population developed from the cross SAF × SAB was analyzed from the parental genotypes to the F4 generation for the segregation of these traits. The variation of glossiness was attributed to two alleles at the
However, the glossiness of the seed coat in Serro Azul is also related to the expression another gene located in chromosome 10 and referred as the
The segregation of the seed coat glossiness along with the color pattern is clearly observed in F2:3 lines (Figure 1A) of the cross SAF × SAB and is only due to the
Another important aspect of the seed coat glossiness of SAB was shown from microscopy analyses. It followed and confirmed previous findings of classic studies of the glossiness of other common bean genotypes. In general, dull genotypes (
The seed glossiness has been frequently neglected in breeding programs due to consumer preferences. This is explained by the fact that glossy seeds tend to require higher cooking times than seeds with an opaque seed coat [21]. At first, it seems that since glossiness retards water absorption by the seeds [12, 22] (check Figure 2), they take longer to be cooked. However, some line of evidence showed no significant correlation between the cooking time and the water absorption rate [23]. Further examination of the genes involved in cooking time is necessary, though.
Water uptake on the course of 480 min of the variants Serro Azul Brilhante (SAB, with glossy seed coat) and Serro Azul Fosco (SAF, with dull seed coat). Three replicates of seeds were embedded in distilled water and paper dried every 30 min for weighing and determining the weight change (adapted from [
It is well known that the seed coat is the structure that protects the seeds from pathogens and insects, and the glossiness seems to have an important role in such protection. Moreover, seeds with glossiness might have enhanced antioxidant properties due to a higher concentration of specific secondary metabolites in the seed coat, therefore, having an impact in human health [12].
Usually, in the case of landraces, where local selection has been performed, it is more frequent to find common bean accessions that show glossy seed coat [24] (checking the list of genotypes) than in breeding programs. In the case of the landrace Serro Azul, both variants Serro Azul Brilhante (glossy) and Serro Azul Fosco (opaque) have been cultivated [11, 13]. Morphological and biochemical findings are hereafter discussed to show advantages of the seed glossiness for aspects related to human health.
The seed coat glossiness has been studied to be mainly conditioned by the
Classical work has suggested that
Proanthocyanidins are oligomers or polymers formed by the condensations of flavan-3-ols units such as catechins and epicatechins [28, 29]. In common bean, condensed tannins are mainly composed of catechin monomers [30]. As secondary metabolites, they play important roles as antioxidants, anticarcinogenic and anti-inflammatory [28, 31, 32].
On the other hand, the
Therefore, although glossiness has been generally neglected by consumers and, as a result, by selection programs, it might have positive implication for human health. Moreover, the indication that glossiness is not necessarily associated with higher cooking time (since there is a lack of correlation between water absorption and cooking time) as shown by Garcia et al. [23] needs to be further explored by the researchers. Landraces such as Serro Azul are one of the sources for rescuing the value of seed glossiness.
One of the most important aspects of a breeding program is to find genotypes that are tolerant or even resistant to diseases. The cultivation of common bean is majorly affected by diseases such as common bacterial blight caused by
Here, we present new findings obtained with experiments conducted with Serro Azul Brilhante and Serro Azul Fosco, as regards their variation for anthracnose resistance. The resistance degree to
The results revealed an interesting difference between the parents SAF and SAB, used to constitute the segregating populations. The detached leaf method clearly showed that SAB was highly resistant to both races studied (65 and 73), while SAF showed high susceptibility to the
Screening for anthracnose resistance with races 65 and 73 (
Genotype | Mean score | |
---|---|---|
Race 65 | Race 73 | |
G2333 (resistant control) | 2 ± 0.8 | 1 ± 0.5 |
Rosinha G2 (susceptible control) | 5 ± 0.4 | 4 ± 0.2 |
SAB | 1 ± 0.0 | 3 ± 0.6 |
SAF | 7 ± 3.0 | 5 ± 1.1 |
Mean comparisons—Tukey’s test | ||
G2333 × Rosinha G2 | p = 0.012* | p = 0.001* |
SAB × SAF | p = 0.0001** | p = 0.081 ns |
Average scores of
Significant at
significant at
The evident difference between SAF and SAB needs further examination. It raises questions such as if the anthracnose resistance is somehow influenced by the glossiness of SAB. After all, genes related to anthracnose resistance are also located in chromosome 7 [40], but a specific study linking
The genetic diversity of common bean landraces, cultivars and wild accessions has been investigated in multiple studies, mainly based on morphological and molecular markers in the last two decades (from 1995 to 2017). In the 1990s, studies have shown high genetic diversity based on morphological, enzyme and DNA-based markers (RAPD and microsatellites) [41, 42, 43]. After 2000, several studies involving amplified fragment length polymorphic (AFLP) [44, 45] and microsatellite [24, 46, 47] markers have been conducted. After 2010, with the advances of the sequencing technology, numerous papers have addressed the molecular diversity of common bean based on SNP markers [4, 48, 49, 50, 51]. In general, most of the studies revealed that common beans are divided into two main gene pools, the Mesoamerican and Andean. In the case of Brazil, where common beans were introduced and have been cultivated mainly in small farming systems, varieties of both pools have been encountered. However, Burle et al. [24] investigated the genetic diversity of almost 300 landraces cultivated in Brazil and demonstrated that almost 80% of the genotypes have a Mesoamerican background, based on a population structure analysis with microsatellite polymorphisms.
In the case of Serro Azul, we also examined the molecular diversity of a sample of plants from both the variants (Serro Azul Brilhante and Serro Azul Fosco) by using the AFLP markers. Selective amplifications were done with four primer combinations (
AFLP profile (primer combination
UPGMA tree based on Jaccard similarity analysis and AFLP profiles of the two variants of the landrace Serro Azul.
The findings about Serro Azul provide interesting insights of the use and application of landraces in common bean breeding. A distinguishable morphologic diversity is noticeable within the landrace, which can be further explored to investigate genes responsible for color and glossiness [12]. SAB and SAF are consistently different at the molecular level as well, as revealed by the AFLP profiles. An examination of AFLP polymorphisms among F4 lines of the cross SAF × SAB revealed a potential discrimination of color classes in the population by the molecular approach [12]. Furthermore, Serro Azul and the population developed might be used to investigate the genetic control for such incredible difference in anthracnose resistance between SAB and SAF. Another interesting observation comes from field observations where the SAF × SAB population was being tested. Usually, lines with similar features to the SAB parental line, especially the seed glossiness, presented very low incidence of bruchid attacks. On the other hand, SAF-derived lines were usually susceptible to the insects, leading to damages to the seeds.
The remarkable variability of Serro Azul and the interesting association with glossy seeds (SAB) with resistance to anthracnose and bruchids raises further research questions and opportunities for new crosses. As previously suggested, seed coat glossiness might after all have an important role in protecting seeds against biotic stresses, as SAB has shown. Conversely, we have not demonstrated that the disease resistance of SAB plants has association with glossiness, which needs more experiments. Either way, this is an important feature which might be explored in depth with the population derived from this landrace to appropriately answer this question. Landraces such as Serro Azul hold particularities that should not be disregarded, after all, local communities need those seeds for their supply, and they have traits of high interest to be explored by breeders, especially concerning the threat of anthracnose and insects to common bean cultivation.
From this example to a wider set of landraces, several traits of interest might be improved with the use of distinct allele combinations if not new alleles provided by such genetic materials. Burle et al. [24] analyzed 279 landraces of common bean from Brazil and discovered considerable genetic diversity among all the accessions evaluated. Those genotypes are distributed from colder to warmer and from wetter to drier areas in the country. The local adaptation implicated in such genotypes has implicated in potential sources of disease and insect-resistant accessions. Moreover, the climatic diversity provides the potential for adapting to distinct abiotic stresses. New sources for tolerance to drought, soil salinity, high and low temperatures are to be investigated from these collections. In fact, Burle et al. [10] continued the previous work and integrated phenotypic evaluations to the genetic analysis of the same 279 landraces. The authors screened these accessions based on 22 morphological traits, including resistance to rust and common bacterial blight, yield, flowering time, determinacy and growth habit, seed coat color and brilliancy, among others. The study provided valorous information for supporting initiatives toward conservation and management of the accessions. It also allowed to detect the particularities of landraces and how they can be explored in controlled crosses for designing new populations and cultivars.
In this chapter, we described the importance of the conservation and study of landraces of common bean. As an example, to go through the extent of morphological, biochemical and genetic aspects of landraces, we outlined the previous results as well as the new findings about the Brazilian landrace Serro Azul. This landrace has been produced by local farmers from Sao Paulo state and has remarkable features for exploring variation of seed and yield traits in common bean, constituting an additional and valuable genetic resource for germplasm collections. We also showed a genetic diversity analysis of Serro Azul by examining the molecular variability within subsamples of SAB and SAF, based on amplified fragment length polymorphic (AFLP) markers. Furthermore, a detached leaf assay for screening anthracnose resistance was employed for both variants within this landrace, revealing remarkable differences between the highly resistant Serro Azul Brilhante (glossy seed coat) and the susceptible Serro Azul Fosco (opaque seed coat). Together, these results demonstrated the importance of studying genetic aspects related to traits such as color, glossiness, disease resistance and yield components. This is necessary to conserve such valuable resources as the ones maintained by small farming systems. It may as well be applicable to other landraces of common bean, in order to provide better understanding of the genetic resources available and how they can be explored in favor of the farmers and breeders.
We thank Monica Rossi Lanzoni and Prof. Adriana Pinheiro Martinelli for their assistance in the microscopy analyses. We also thank the assistance and materials provided by the Agronomic Institute of Campinas for performing the analyses with the races of
The authors declare no conflicts of interest.
According to the US National Institute of Health, drug delivery is a process that permit the influx of therapeutic substances in to the body. Drug delivery systems are designed to enhance the efficiency and safety of therapeutics by regulating the rate, time and place of release in the body [1, 2]. Drug delivery technology has emerged as an essential tool for the improvement of drug bioavailability, reduction in the side effects of medication, all of which generate remarkable clinical outcomes [3]. Drugs may be administered to the body via local application, enterally or parenterally. The parenteral route typically relates to administration that excludes absorption from the gastrointestinal tract (GIT). It consists of administration by injection, inhalation and via transdermal routes. The enteral route is associated with the absorption of the drug via the GIT, this includes oral, sublingual, and rectal administration. Aptly, the mode of drug administration depends on the disease, the desired therapeutic effect and the nature of the product available [4]. Moreover, each delivery route has inherent benefits and constraints. Nevertheless, the majority of manufactured medicines in the pharmaceutical industry are delivered orally, owing to the distinctive advantages offered by this route, including versatility in accommodating various types of drugs, simplicity of administration and accessibility, patient compliance and safety profiles [5, 6, 7]. Additionally, the intestinal epithelium is an ideal platform for drug absorption due to the viscous mucosal layer lined with abundant enterocytes, goblet cells, and Peyer’s patches that trap drug molecules within the mucus as they transit the GIT. [8, 9].
In comparison to other routes of administration, the oral route is exceptionally complex in expression of anatomical features physiology throughout the GIT [10]. Furthermore, these expressions vary along the GIT in both intensity structure. For example, the mucus layer varies in composition and physical properties along the GIT and the pH varies significantly in the main sections of the GIT. The gastrointestinal motility also varies in intensity and form along the GIT and also depends on food status [11]. Even though, these features can impede drug delivery across the GIT, through careful interplay between formulation science and GIT physiology, scientists have been able to exploit this variance for improved drug delivery. In this regard, nanoparticle formulations have immerged as strong contenders able to surmount some of the constraints associated with GIT absorption. Nanoparticles have gained great interest by researchers in recent years as they can be used to improve drug solubility and bioavailability in the harsh GIT environment due to increased surface area to volume ratio, thus provide a rapid onset of therapeutic action [12]. They can also be used to targeting specific sites within the GIT and hence reduce the effects of enzymatic degradation, all of which can improve the safety and effectiveness of drugs [12, 13].
Nanoparticle formulations may be presented in various forms however, polymeric nanoparticles present the versatility of polymers and can be tailored to achieve superior drug stability, enhanced drug payload capacity, longer circulation times and controlled drug release capabilities, when compared with other their colloidal counterparts [14, 15]. In this regard, chitosan-based nanoparticle formulation have been shown to present several of the desirable attributes listed above in addition to being biodegradable, having low toxicity, amenable to tuneable physical properties and bio-adhesive properties [16, 17].
In this chapter we will be discussing the interplay between the GIT physiology/anatomy and drug physicochemical/biopharmaceutical factors in the absorption process that influence oral therapeutics. We, will also review the physicochemical properties of chitosan relevant for effective GIT delivery, including methods of formulation. The most utilised nanoparticle formulation methods used for chitosan-based nanoparticles are also examined. Finally, we will highlight the recent developments on chitosan-based nanoparticles used in the oral delivery of different drugs.
The GIT, also known as the digestive tract or alimentary canal, is approximately 9 meters long and can be functionally divided into two parts, the upper and the lower GIT (Figure 1). The upper GIT; consisting of mouth, pharynx, oesophagus, stomach and small intestine, play a major role in the transport of the swallowed food bolus, enzymatic digestion and absorption of nutrients [18]. The lower GIT is usually referred to the large intestine and is responsible for the adsorption of water, fermentation of undigested sugars and the storage and evacuation of stool [19]. Following oral dosing, the drug traverses several semipermeable cell membranes through its trajectory to absorption and eventually enters the general circulatory system. Drugs cross cell membranes, which comprise of bimolecular lipid matrix, either by passive diffusion or active transport.
The anatomy of the human gastrointestinal tract.
The most prevalent form of absorption of the majority of orally administered drugs is by passive diffusion across cell membranes. This process comprises of a three-step process, whereby the permeant first transverses into the membrane, disperses across it and then is released into the cytosol [20]. Typically, drug molecules move down a concentration gradient, from a region of high concentration (e.g., GI fluids) to one of low concentration (e.g., blood), without the expenditure of energy [21]. Usually, a concentration gradient is manifested as a disparity in concentration of a substance within an area and is linearly related to the diffusion rate. The latter is also governed by the lipid solubility, size and polarity of the drug species.
Most drugs are either weak acids or bases and occur either in the unionized or ionized form as a function of pH [22]. For lipophilic drugs, the unionized form of drug, may penetrate cell membranes easily as the membrane is lipoidal. On the other hand, hydrophilic drugs, present an ionized form of the drug, which has high electrical resistance and thus cannot traverse the cell membranes easily but may diffuse through the para-cellular spaces. However, it is worth noting that the para-cellular junctions contribute to less than 0.01% of the entire GIT surface area and furthermore, the permeability of these junctures diminishes down the GIT [23]. Additionally, the capability of drugs to traverse a membrane also relies on the acid–base dissociation constant (pKa) of the drug in question. The pKa is the pH at which concentrations of ionized and unionized forms are equivalent [24]. So, if the pH is less than the pKa, the unionized form of a weak acid prevails, and
Overall, the process by which molecules traverse cell membranes is by passive diffusion, down the concentration gradient. However large hydrophilic ionic molecules and charged molecules cannot freely traverse the phospholipid bilayer cell membrane passively. Their transport may be confined to protein channels and distinct transport mechanisms present within the membrane [25]. Such drugs gain access through the membrane by facilitated diffusion whereby molecules integrate with embedded protein carriers to shuttle them across the membrane. This process does not expend energy and is also down the concentration gradient though quicker than would be anticipated by diffusion alone [26]. A frequent case of facilitated diffusion is the migration of glucose into cells during the production of adenosine triphosphate (ATP). Glucose is both large and polar thereby unable to pass the lipid bilayer via simple diffusion. Hence, glucose molecules are delivered into the cell via a unique carrier protein (glucose transporter) to promote its internalisation in cells [27].
Active transport is an energy-dependent process that translocates drug molecules against their concentration gradient by a molecular pump [20]. Carrier-mediated active transport demand energy via ATP hydrolysis or by accompanying the co-transport of counter ions down its electrochemical gradient (e.g., Na+, H+, Cl−) [28]. The most common active transport system is the sodium-potassium pump and receptor-mediated endocytosis. Energy can either be directly provided to the ion pump or indirectly by connecting a pump-action to an activated ionic gradient. It is often encountered in the gut mucosa, the liver, renal tubules and the blood–brain barrier [22]. Active transport is typically restricted to drugs that structurally resemble endogenous substances; e.g., vitamins and amino acids, and that are absorbed via specific sites in the small intestine. Targeting drugs to these transporters can enhance their bioavailability and distribution [21].
The sodium-potassium pump system (Na+/K+ ATPase), utilises ATP to move Na+ and K+ in and out of the cell. It is a vital ion pump located in the membranes of various cell types, such as the Na+/amino acid symport in the mucosal cells of the small bowel [22, 29].
Cells control the endocytosis of certain substances via receptor-mediated endocytosis. The use of this form of endocytosis in the GIT is crucial for oral delivery of drugs because it delays the transit of drugs in GIT. Receptor-mediator endocytosis involves the internalisation of macromolecules by binding the latter to receptors considered as membrane-associated protein [30]. There are more than 20 different receptors involved in the internalisation of macromolecules [31]. Following binding to the receptor on the cell surface, the cell will endocytose the portion of the cell membrane enclosing the receptor-ligand complex via a clathrin-dependent endocytic process [28]. Clathrin plays a significant role in the formation of clathrin-coated pits; invaginated regions of the plasma membrane, and pinch off to form clathrin-coated vesicles that transport molecules within cells [31].
In summary, drug adsorption may occur passively or via active transport. In either case, absorption occurs predominantly in the small intestine due to its more permeable membrane and larger surface area provided by the microvilli. Even though, the stomach has a relatively broad epithelial surface, yet the dense mucus layer and transient transit times expended by dosage forms contribute to an impeded absorption. Moreover, the colon with an absorptive surface area of about 5m2 has negligible contribution to drug absorption in GIT, due to slow caecal arrival times of dosage forms, the presence of numerous gut bacteria and solid stool that impede lateral diffusion. All in all, absorption of oral drugs is interlinked and controlled by various intrinsic factors; like drug solubility, dissolution and permeability across the mucosal barriers, and physiological factors; such as gastrointestinal transit time, pH and gut microbiome [13, 32].
Drug dissolution, solubility and permeability are the three fundamental parameters used in the Biopharmaceutics Classification System (BCS) to predict the factors limiting drug absorption from GIT [33]. The BCS is recognised as a useful tool for designing drug delivery systems and is adopted by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the World Health Organization (WHO) [34]. According to the BCS, all drug substances are classified into four categories: class I—high soluble and high permeable, class II—low soluble and high permeable, class III—low soluble and high permeable and class IV—low soluble and low permeable [35].
Drug solubility is crucial outcome in pharmaceutical dosage form. In the BCS system, a drug is deemed highly soluble when the maximal dose strength is soluble in 250 mL of aqueous media across the pH range of 1 to 7.5 [35]. However, more than 40% of the established new chemical entities in the pharmaceutical sector are considered insoluble in water, causing inadequate bioavailability [36]. This makes solubility amongst the most important rate limiting parameters in GIT absorption.
Drug dissolution reflects a dynamic consequence to drug absorption [33], whereby drug is released, dissolved and made accessible for absorption. With the exception of enteric formulations and drugs with low acid solubility, the dissolution process for majority of drugs starts in the stomach where the volume of gastric fluid is sufficient to attain effective drug dissolution [37]. Thus, the gastric fluid containing the disintegrated immediate-release dosage forms brings the solubilized drug into contact with the absorptive surface of the small intestine as absorption in the stomach is generally minimal.
Drug permeability represents the final frontier in the sequence of rate-liming steps to systemic drug availability. It is a measure of the ease of permeation of the drug across the intestinal wall. There is a positive association between the intestinal permeability and drug solubility GI milieu, which in turn depends on the physicochemical characteristics of the drug [38], including the pKa, particle size, lipophilicity, as discussed in the sections below. The ultimate amount of drug absorbed from the GIT also bears dependence on its transit time in the GIT [39].
The GI pH influences the extent of ionization of drug molecules and thereby impacts on its absorption across the epithelium. Variations in pH across the GIT can be exploited for delayed drug release in desired section of the GIT in order to achieve efficient absorption. The fasted stomach is acidic, with pH range of 1–3, which increases upon food or liquid intake. Food is known to buffer the acidic content of the stomach. A rise in pH resumes in response to the continual gastric secretion and then finally, the pH reverts to the original levels due to gastric emptying of content; [40]. The gastric emptying rate significantly affects the rate of drug absorption because it regulates arrival in the duodenum, where the epithelial surface is suited for absorption [41]. Moreover, the disparity in gastric pH conditions affects the drug delivery behaviour of modified release dosage forms such as enteric coated products, where the onset of release along with the overall release kinetics may be changed [42].
The arrival of orally administered dosage forms into the small intestine is met by a pH of about 6 in the duodenum through to pH 7.4 at the terminal ileum [43]. This high pH variability is due to duodenal secretion of alkaline bicarbonate. During postprandial state, the initial intestinal pH drops due to the influx of acidic chyme, which is buffered by bicarbonate secretion as it travels distally [13]. Besides, the mean pH in proximal small intestine during the first hour of transit is usually 6.6, which is further decreased to 5–6 in the distal duodenum [44].
Typically, the pH in the caecum drops to just below pH 6 owing to the fermentation processes of the colonic microbiota and then rises to pH 7 at the rectum [42]. The drop in the amount of short chain fatty acids at the distal colon causes the secretion of colonic mucosal bicarbonate that leads to a neutral pH. Short chain fatty acids are the end products of fermentation of dietary fibres by the anaerobic intestinal microbiota [45]. As a consequence of the neutral pH of the colonic luminal fluid, the solubilisation of drug is the rate-limiting factor in colonic drug absorption [46]. The unspecific interactions of drugs with colonic content (e.g. dietary residues, intestinal secretions or faecal matter) all adds to the odds of effective adsorption across the colon [47].
Generally, the GIT transit time of most orally administered doses through buccal cavity and oesophagus is transient. The stomach is naturally the first segment of the GIT, wherein disintegration and dissolution of solids such as drugs and formulations occur [42]. The period required for a dosage form to exit the stomach is inconstant and relies on several physiological factors, such as age, body posture, gender and food intake [48]. Gastric transit can span from 0 to 2 h in the fasted state and can be extended up to 6 h after food intake [47]. The small intestine is the region of choice for drug absorption with a transit time ranging from 2 to 6 h in healthy individuals. The dissolution of poorly soluble, weakly acidic compounds and lipophilic compounds is greatly enhanced in this region [13]. In colon-specific drug delivery, the drug has to cross the whole GIT prior to arrival at the colon. Thus, the transit time across the colon can be highly variable, and ranges from 20 to 56 h in healthy humans, although higher variations are also reported in literature amounting up to 72 h [42, 49, 50]. Variations in colonic transit time are affected by dosing time, bowel movements as well as gender, whereby females generally have longer colonic transit times than males [51, 52].
Enzymatic and microbial degradation of GIT content affects the amount ultimately made available for absorption. The active sites for most endogenous enzymes are the stomach and small intestine. Even though these enzymes may affect the stability of orally administered drugs, it is possible to exploit this property for regional drug delivery of formulations in the GIT [47]. On the other hand, the intestinal microbiome which includes 500–1000 bacterial species is also important for the digestion of food and the metabolism of drugs [53]. Gastrointestinal microbiome is found in both upper and lower GIT, whereby, a lower bacterial number (1013–1014 bacteria mL−1 of intestinal content) is in the upper GIT because of the fast luminal flow, intestinal fluid volume, and the secretion of bactericidal compounds in this part of the GIT, and highest bacterial community (1010–1011 bacteria mL−1 of intestinal content) is in the colon, in which the redox potential is low and the transit time is long [54, 55]. Therefore, greater number of the intestinal microbiome exists in the anaerobic colon, in which the fermentation of carbohydrates contributes to their nourishment. Usually, orally administered drugs are transformed to bioactive, bio-inactive, or toxic metabolites by the gut microbial population, all of which can impede the bioavailability of drug. However, gut microflora can improve drug bioavailability by eliminating polar moiety from derived conjugates and thereby promoting biliary recycling of compounds [13].
Thus, formulation scientist must be cognizant of the interplay between drug and physiological and anatomical manifestations within the GIT when designing orally administered dosage forms. For example, enteric coating can be applied to dosage forms to delay the release of the API in the acidic gastric fluid until pH above 5.0 [56]. Enteric coating may also be used to shield acid-labile drugs from gastric distress, and upon arrival to the alkaline pH milieu, the enteric polymer coating disintegrates within the intestinal fluid, releasing the drug [57]. Despite employing such coatings and other conventional interventions, numerous pharmaceuticals still display insufficient bioavailability through the oral route of administration. This necessitates the use of alternate strategies. One area of research that is gaining traction more recently is the employment of nanoparticles.
Nanoparticle technology is a multidisciplinary field that utilizes principles from chemistry, biology, physics and engineering to design and fabricate submicronic (< 1 μm) colloidal systems [58]. Nanotechnology has several pharmaceutical and medical applications wherein nanoparticles (NPs), with sizes comparable to large biological molecules such as enzymes can be employed in the delivery of therapeutic agents [59]. The effectiveness of the nanoscale drug delivery vehicles lies on their ability to attain the following key attributes [60]:
The NP must be able to bind or contain the appropriate drug.
The nanocarrier must stay stable in the serum to allow systemic delivery of the therapeutics and only release the drug once at the required site.
The NP-drug complex has to reach the required site either via receptor-mediated interactions or by the enhanced permeability and retention (EPR) effect.
The residual NP carrier should ideally be made of a biological or biologically inert material with a limited lifespan to allow safe degradation.
There are several types of NP drug delivery systems, which may be broadly divided as organic and inorganic NPs [61]. Their particle size, surface charge (ζ potential), hydrophilicity/hydrophobicity, composition, etc. can be tailored for a diverse applications [62]. The primary consideration when designing orally administered NP drug delivery system is to maximise drug concentration in the GI therapeutic window.
Organic NP (Figure 2) are solid particles comprised of organic compounds (usually lipidic or polymeric) ranging from 10 nm to 1 μm [63]. They can be formulated by simple techniques to encapsulate therapeutic agents. Preferably, compounds used in formulation of organic NPs should be biodegradable and biocompatible [61]. Manifestations of organic NP include liposomal, polymeric and solid lipid NP, each system possessing requisite features that addresses physiological and anatomic constraints addressed in sections above. In addition, others systems such as micelles, dendrimers etc. have been also explored as effective nanocarriers for effective deployment of APIs in the GIT [14, 64].
Examples of organic nanoparticle platforms for drug delivery.
Inorganic NP represent a wide spectrum of systems synthesized from metals, metal oxides, and metal sulphides [65]. Gold, silica and superparamagnetic oxide NP are among the long list of inorganic NP (Figure 3). They have been studied for use in imaging on nuclear magnetic resonance and high-resolution superconducting quantum interference devices, and their intrinsic properties have been utilised for therapy [66]. Inorganic NP can easily be conjugated to ligands for tumour targeting and/or with chemotherapeutics for tumour therapy. Additionally, their surface composition can be feasibly manipulated to create NP that can escape the reticuloendothelial system [67]. Even though inorganic NP present good stability characteristics, they have not been the focus of attention in oral NP research, possibly due to concerns on the degradation and elimination end products, which can be potentially toxic [68].
Examples of inorganic NP platforms for drug delivery.
Generally, inorganic NPs differ conceptually from organic NPs in terms of fabrication principles. Inorganic NPs can be formed by the precipitation of inorganic salts, which are linked within a matrix, whilst, most organic NPs are formed by several organic molecules through self-organization or chemical binding [61]. Notwithstanding, both types of NP are very promising in the formulation of oral delivery system and forms part of the evolutional success in several clinical applications. Polymeric NP arguably presents more desirable attributes as orally delivered NP because of their higher stability, enhanced drug payload and controlled drug release capabilities compared with their colloidal counterparts [14, 69].
According to Alexis F. et al., polymeric NP represent the most effective nanocarrier system for prolonged drug delivery [70]. ‘Polymeric NPs’ include any type of polymer formed as NP. Nanospheres are solid spherical NP with molecules attached or adsorbed to their surface, whilst nanocapsules are vesicular systems with substances confined within a cavity consisting of a liquid core (either water or oil) surrounded by a solid shell [71]. Characteristic properties of polymers such as molecular weight, hydrophobicity and crystallinity can be explored to manifest controlled drug release kinetics and entrapment of therapeutic agents [72]. Polymers also provide significant flexibility in the design of oral NP and many exhibit biodegradability [73]. In this regard, synthetic and natural variants have been studied. For example poly-lactic-co-glycolic-acid (PLGA) and poly-lactic-acid (PLA) are synthetic whilst natural polymers include gelatine, dextran, and chitosan [74]. The use of natural polymers is preferred over the synthetic ones as the former usually exhibit less toxicity, widely available and have lower production costs [75]. Chitosan is arguable one of the most studied polymer in NP formulation in view of its distinctive properties. In orally administered NP, chitosan offers added desirability including muco-adhesiveness, augmenting the dissolution rate of poorly water-soluble drugs; useful in drug targeting in the GIT [76].
Chitosan is a hydrophilic, cationic polysaccharide soluble in dilute acids such as acetic acid and formic acid, due to protonated amine groups (NH3+) [75]. It is an N-acetylated derivative of chitin, a natural polysaccharide found in the shells of marine crustaceans. Chitin is chemically inert and thus has fewer applications that chitosan [77]. The acetamido group of chitin, (C2H4NO) can be turned into amino group to yield chitosan by the alkaline deacetylation of chitin. Chitosan is approved as safe by the United States Food and Drug Administration (US-FDA) for dietary use and wound dressing applications, but its toxicity increases with electrical charge and degree of deacetylation [17]. Chemically, it comprises of β- [1–4] -linked D-glucosamine and N-acetylated units (Figure 4).
Chemical structure of chitosan, comprising N-acetyl-D-glucosamine (right) and D-glucosamine (left) units.
The amine group has pKa of 6.2–6.5 [78]. At slightly acidic pH values, the amine groups (NH3+) become protonated, hence possessing the ability to effectively form electrostatic interactions with negatively charged species within mucin in the GIT [75]. Positively charged moieties of chitosan also interact with the tight junctions of the intestinal epithelial cells and thus modulate drug permeation and absorption through the interstitial space between epithelial cells [79]. Moreover, the existence of both hydroxyl and amino groups offers various possibilities for chemical modification. Chemical modifications give rise to different functional derivatives of chitosan like carboxylation, thiolation, alkylation, acylation etc. that further imparts desirable physiochemical and biopharmaceutical properties, such as solubility, adsorption and pH sensitivity in oral drug delivery [80]. For example, N-trimethyl chitosan chloride is developed to amplify the intestinal solubility of chitosan; thiolated chitosan is produced to augment the mucoadhesiveness of chitosan; quaternization of chitosan reinforces its impact on the tight junctions of the GIT epithelium whilst grafting carboxylated chitosan with poly(methyl methacrylate) imparts increased pH sensitivity [81]. Physical modification through blending with other polymers may be used to enhance desirable physical properties. For example, blending of chitosan with polyethylene glycol (PEG) and polyvinyl alcohol (PVA) ameliorate the hydrophilic property of chitosan, while blending of chitosan with cellulose improves its antibacterial properties [82].
Some of the key desirable features in orally administered dosage forms is delayed GI transit in the duodenum and ability to traverse the epithelium effectively. In this regard, chitosan-based NP have been shown to possess these attributes. Mucoadhesion refers to the adhesion between two materials, one of which is mucosal [83]. It can be utilised to prolong the GI transit of dosage forms in the duodenum, thereby improving bioavailability. Delayed transit results from interactions of positively charged moieties in chitosan with negatively charged moieties in sialic acid within mucin [81]. Chitosan is also capable of physically penetrating the mucous network. Prolonged GI residence results in higher net drug flux across the GIT membrane. Drug flux is a combination of passive diffusion and uptake of whole NP by Peyer’s patches [84]. Moreover, chitosan offers controlled drug release capabilities via diffusion from the matrix. Yin et al. prepared thiolated trimethyl chitosan NP for the oral delivery of insulin, where increase in the mucoadhesion resulted in increased insulin transport through rat intestine and uptake by Peyer’s patches compared to controls. They attributed these results to the disulfide bond formation between the NP and mucin [85]. Overall, to achieve the desired properties of interest such as particle size, particle size distribution and area of application, the mode of preparation of chitosan NP plays an essential role.
The preparation of chitosan NP is principally divided into two approaches. The first approach is based on a two-step procedure, where an emulsification system is carried out to generate nanodroplets in which organic compounds (polymer, monomer, and lipid) are solubilized, followed by precipitation or polymerisation into NP [61]. The second approach involves a one-step procedure where the NP are directly generated via different mechanisms such as nanoprecipitation or ionic gelation [86]. An example of each of the two general approaches is summarized in the following.
Ionic gelation, also known as ionotropic gelation or polyelectrolyte complexation involves the gradual addition of a cross-linking agent (tripolyphosphate, glutardehyde etc.) into an aqueous solution of chitosan under continuous stirring to form hydrogels [87]. The polyanions from the cross-linker forms a meshwork of structures by interacting with the polyvalent cations within chitosan, leading to gelation [88]. APIs can be loaded into these hydrogels during the production where it becomes encapsulated or added to the formed NP, where it can be adsorbed into the matrix. The choice of the cross-linker should be matched to the desired physical characteristics of the NP, such as mechanical strength, as well as safety profiles. For example, glutardehyde reported to be toxic when used in high concentrations and results in NP with low mechanical strength. This has been attributed to its double bond (–C=N–) association with the amine group in chitosan [89]. Genipin is a natural cross-linker obtained from iridoid glucoside (geniposide) and present in gardenia fruits that can be cross-linked with chitosan. It displays slower degradation rate than glutaraldehyde and possess higher biocompatibility. Sodium tripolyphosphate (STPP) displays better crosslinker characteristics than each of the above because of its inorganic nature and consequently, results in production of chitosan NP with better mechanical stability. The size dimension derived from STPP gelled chitosan NP is of lower order as well. Another attractive feature of STPP is that it is nontoxic, relatively inexpensive, multivalent, has quick gelling property and thus, widely utilised as a crosslinker in chitosan-based NP [90, 91, 92].
Polymeric nano-emulsions are formulated whereby organic solvent is added to a solution of chitosan with surfactant and mixed via sonication [93]. Basically, the emulsion droplets are converted into NP suspension as the organic solvent evaporates by continuous magnetic stirring at room temperature. The NP suspensions are then centrifuged, washed with distilled water to remove additives such as surfactants and finally lyophilized [94]. Poovi et al. encapsulated the poorly water-soluble drug, repaglinide, into chitosan NP using the emulsion evaporation for sustained release. They proved that the NP exhibited a controlled release of repaglinide and obtained a high drug loading (11.22% w/w) and encapsulation efficiency (97.0%) [95]. In another study, Lee et al. employed solvent evaporation method to formulate polymeric NP from chitosan derivatives fluorescein isothiocyanate (FITC) - conjugated glycol CSs (FGCs) using diluted chloroform as the solvent. Size range of 150–500 nm were obtained and the NP remained stable in phosphate buffered saline for 20 days at 37°C [96].
As mentioned in sections 4.1 and 4.2, extensive research presented the potential of chitosan as an oral absorption enhancer owing to its mucoadhesive properties and ability to loosen tight junctions within the GI epithelia, hence permitting the passage of macromolecular therapeutics across a “well-organised” epithelia [100]. Moreover, due to various characteristics; i.e. non-toxic, biodegradable, biocompatible, antimicrobial property etc. [104], chitosan NP hold promise as a suitable oral delivery vehicle for a wide spectrum of therapeutics including, anti-cancer drugs, antibacterial agents, polyphenolic compounds and protein drugs.
Chemotherapeutic APIs usually exhibit low bioavailability following oral administration. Several studies have investigated chitosan-based NP as a possible delivery system to address this issue. For example, doxorubicin (Dox), broadly employed to treat breast, bladder and other cancers, is typically delivered intravenously. The oral bioavailability of Dox is low due to efflux transporter P-glycoprotein, which identifies Dox as a substrate, restraining its cellular uptake [105]. In 2013, Feng et al. developed chitosan/o-carboxymethyl chitosan (CS/CMCS) NP as a pH responsive carrier for the oral delivery of Dox. They investigated the bioavailability of orally administered Dox-CS/CMCS NP and free Dox drug on Sprague–Dawley rats. Negligible Dox was detected in plasma after the oral dosage of free Dox, representing its poor absorption. On the other hand, 2.3-folds increase in plasma concentration of Dox was registered after an oral dose of Dox-CS/CMCS NP. Moreover, accumulation of Dox in the liver, spleen and lungs were demonstrated in rats treated with oral Dox- CS/CMCS NP, as opposed to DoX solution which was more concentrated in the kidneys. They concluded that the NP matrix improved the intestinal absorption of Dox and thus improved oral bioavailability [106].
Gemcitabine (Gem) is a widely prescribed anticancer agent used in pancreatic, lung and advanced colon cancer. Oral administration of Gem results in low oral bioavailability, high first-pass clearance gastrointestinal toxicity, such as nausea, vomiting and diarrhoea [107]. Hosseinzadeh et al. synthesised and characterised chitosan/Pluronic® F-127 (Gem-Chi/PF) NP in oral delivery of Gem for the treatment of colon cancer.
Chitosan impedes the growth of bacteria, fungi, and yeast [109]. It exhibits potential antimicrobial properties at pH below 6.0 because of the positively charged – NH3+ at the C-2 position within the glucosamine. Low molecular weight chitosan derived NP integrate with bacterial DNA, impeding mRNA synthesis. Conversely, the NH3+ in high molecular chitosan derived NP interact with the negatively-charged cell wall in microorganisms and subsequently amend cell permeability [110]. Alqahtani et al. formulated chitosan NP from high and low molecular weight variants to encapsulate the non-antibiotic diclofenac sodium (DIC). The antibacterial properties of NP from low and high molecular weight of chitosan on
Secondary plant metabolites in the form of polyphenolic compounds have gained wide attention by scientists due to their wide spectrum of pharmacological activities, including antioxidant, antimicrobial and anticancer properties. Most however suffer from poor systemic bioavailability following oral administration due to low solubility and susceptibility to GI degradation. To overcome this constraint, chitosan-based NP have been proposed as a possible delivery intervention, which not only protect these APIs from GI degradation but also improves bioavailability [112]. Curcumin (CUR) is a polyphenol that has been studied extensively. It is derived from the rhizomes of
Proteins are the building blocks of life and required in replicating organisms. Their high molecular weight, chemical and enzymatic susceptibility in the GIT, low diffusion rate through the mucosa barrier and fast systemic clearance, limit their delivery via oral route. As a result, most proteins are administered parenterally. Fortunately, chitosan-based NP are emerging as promising means for the delivery of protein drugs by the oral route through a combination of shielding GI pH, enzymatic degradation and facilitation of epithelial uptake [117]. In a study by He et al., chitosan-STPP insulin NP (CS/STPP/insulin) were orally administered to Type I diabetic rat models in comparison to free insulin solution. Free insulin solution failed to elicit any difference in the blood glucose level, whilst CS/STPP/insulin NP distinctly reduced the blood glucose levels by up to 59% within 8 hours. Crucially, CS/TPP/insulin NP allowed for a fast recovery of blood sugar level when fasting was halted. Moreover, the CS/TPP/insulin NP exhibited negligible toxicity to liver enzymes, confirming the safety profile of the orally delivered CS/TPP/insulin NP. They concluded that CS/TPP NP are an effective oral delivery vehicle for insulin [118]. In another study, Tan et al. demonstrated better
The oral route of administration remains formidable in the systemic delivery of therapeutics. It affords patient compliance, ease of administration and flexibility and remains the favourite choice for administration by patients. However, orally administered therapeutics may undergo premature release in the upper GIT which may render them to enzymatic or pH degradation. Therapeutics that are delivered to the absorptive window are susceptible to efflux pump and metabolic enzymes (e.g., cytochrome P450 enzymes) within the GIT epithelia, which is itself a structural barrier. Scientist involved in the design of therapeutics intended for GI delivery must be cognizant of the above constraints and balance these with the physicochemical properties of the therapeutic. Recent evidence attest to the fact that appropriately formulated NP may be fit for this pursuit. In this regard, chitosan NP is the subject of intense interest because it is readily available, biocompatible, biodegradable, mucoadhesive and influences traversing of therapeutics across the GI epithelia. We expect to see more evidence on the application of chitosan in the oral delivery of therapeutics, especially in the form of NP. Further studies on toxicity related issues
These Terms and Conditions outline the rules and regulations pertaining to the use of IntechOpen’s website www.intechopen.com and all the subdomains owned by IntechOpen located at 5 Princes Gate Court, London, SW7 2QJ, United Kingdom.
',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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\n\nThe following terminology applies to these Terms and Conditions, Privacy Statement, Disclaimer Notice, and any or all Agreements:
\n\n“Client”, “Customer”, “You” and “Your” refers to you, the person accessing this website and accepting the Company’s Terms and Conditions;
\n\n“The Company”, “Ourselves”, “We”, “Our” and “Us”, refers to our Company, IntechOpen;
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. 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Mainly, type FAdV-4 is responsible for hydropericardium hepatitis syndrome (HP), type FAdV-1 for gizzard erosion and ulceration (GEU), and types FAdV-2, 8a, 8b, and 11 seem to be responsible for inclusion body hepatitis (IBH). Defining the spreading of the avian adenovirus strains in different types of fowl profile production, recognising their property and determining their types and molecular characterisation are very important from the epidemiological point of view and are considered as excellent basis for vaccine development and gene therapy implementation. This chapter provides a comprehensive review of FAdVs, including their epidemiology, pathogenesis, diagnostic, detection, and molecular characterisation. This comprehensive review is needed to better understand the latest progress in study of the viruses and prospects regarding disease control and implementation of gene therapy.",book:{id:"6623",slug:"application-of-genetics-and-genomics-in-poultry-science",title:"Application of Genetics and Genomics in Poultry Science",fullTitle:"Application of Genetics and Genomics in Poultry Science"},signatures:"Jowita Samanta Niczyporuk",authors:[{id:"212649",title:"Dr.",name:"Jowita Samanta",middleName:null,surname:"Niczyporuk",slug:"jowita-samanta-niczyporuk",fullName:"Jowita Samanta Niczyporuk"}]},{id:"65864",title:"Poultry Housing and Management",slug:"poultry-housing-and-management",totalDownloads:3177,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Majority of the people in the poorest regions of the tropics rely on poultry production as their major source of protein supply. However, poultry production is hindered by the harsh environmental conditions in this regions therefore, reducing the daily supply of protein. It is believed that understanding heat stress in birds by paying detail attention to the sources of heat generation in a poultry house can help manage the heat stress situation in this region. This text reviews the internal climatic conditions of the poultry houses, how the birds respond to them, and their implications for heat management in poultry production. Thus, it provides pertinent information for guidance on parameters for open poultry houses architectural design that ensures optimum climatic conditions that will alleviate heat stress problem in poultry production in hot and humid climate.",book:{id:"8470",slug:"poultry-an-advanced-learning",title:"Poultry",fullTitle:"Poultry - An Advanced Learning"},signatures:"Ayodeji Oloyo and Adedamola Ojerinde",authors:[{id:"273409",title:"Mr.",name:"Ayodeji",middleName:null,surname:"Oloyo",slug:"ayodeji-oloyo",fullName:"Ayodeji Oloyo"},{id:"274920",title:"MSc.",name:"Adedamola",middleName:null,surname:"Ojerinde",slug:"adedamola-ojerinde",fullName:"Adedamola Ojerinde"}]},{id:"61583",title:"Domestication and Welfare in Farmed Fish",slug:"domestication-and-welfare-in-farmed-fish",totalDownloads:1670,totalCrossrefCites:4,totalDimensionsCites:16,abstract:"The domestication of fish species is still in its early stages when compared to terrestrial animals. The effects of domestication on welfare of farmed fishes are complex to study because fish differ from livestock in genetics, physiology and behaviour, and experience different sensory worlds. Consequently, empathy with fish and understanding of their needs becomes more problematic than with land animals. Additionally, the acknowledgement and study of mental dimensions of fish existence is very recent. We discuss that higher levels of domestication in fish do not necessarily correspond to better welfare because (1) artificial selection by the aquaculture industry is mostly focused on production-related traits such as growth, and this selection process may have unknown negative effects on welfare-related traits; (2) the number of fish species presently farmed (circa 300) is 10-fold higher than land animals, rendering the establishment of standard welfare guidelines extremely complicated; (3) the current paradigm of the Five Freedoms guiding welfare is out-dated and was designed for livestock; and (4) there are still severe knowledge gaps in the biology of farmed fishes, especially in welfare-related traits. The implementation of humane farming systems should integrate industry, science and ethics in an open dialogue in order to produce relevant results.",book:{id:"6053",slug:"animal-domestication",title:"Animal Domestication",fullTitle:"Animal Domestication"},signatures:"João L. 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Besides their adverse health effects and the decrease in production rate, concerns over their importance in public health is still under debate. Decontamination approaches to reduce mycotoxins in feed are technologically diverse and based on chemical, biological and physical strategies. Chemical remediation strategies involve the conversion of mycotoxins via chemical reactions. Biological strategies involve various substances such as plant ingredients, enzymes and microorganisms. Physical processes include sorting, milling, dehulling, cleaning, heating, irradiation or combinational approaches. 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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. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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