List of SLNs and their different ligand conjugated forms for lungs cells targeting.
\\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:"6109",leadTitle:null,fullTitle:"Mobile Robots: Perception & Navigation",title:"Mobile Robots",subtitle:"Perception & Navigation",reviewType:"peer-reviewed",abstract:"Today robots navigate autonomously in office environments as well as outdoors. They show their ability to beside mechanical and electronic barriers in building mobile platforms, perceiving the environment and deciding on how to act in a given situation are crucial problems. In this book we focused on these two areas of mobile robotics, Perception and Navigation.\r\nThis book gives a wide overview over different navigation techniques describing both navigation techniques dealing with local and control aspects of navigation as well es those handling global navigation aspects of a single robot and even for a group of robots.",isbn:null,printIsbn:"3-86611-283-1",pdfIsbn:"978-953-51-5804-2",doi:"10.5772/36",price:159,priceEur:175,priceUsd:205,slug:"mobile_robots_perception_navigation",numberOfPages:706,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"8118f1daeb4d79aa1a234ae61a1fbf55",bookSignature:"Sascha Kolski",publishedDate:"February 1st 2007",coverURL:"https://cdn.intechopen.com/books/images_new/6109.jpg",numberOfDownloads:94571,numberOfWosCitations:43,numberOfCrossrefCitations:42,numberOfCrossrefCitationsByBook:5,numberOfDimensionsCitations:75,numberOfDimensionsCitationsByBook:5,hasAltmetrics:0,numberOfTotalCitations:160,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 1st 2017",dateEndSecondStepPublish:null,dateEndThirdStepPublish:null,dateEndFourthStepPublish:null,dateEndFifthStepPublish:null,currentStepOfPublishingProcess:1,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"150980",title:"Dr.",name:"Sascha",middleName:null,surname:"Kolski",slug:"sascha-kolski",fullName:"Sascha Kolski",profilePictureURL:"https://mts.intechopen.com/storage/users/150980/images/system/150980.jpg",biography:"I'm Sascha Kolski, I was working on my PhD thesis at the Autonomous Systems Lab at the Swiss Federal Institute of Technology (ETHZ) in Zurich, Switzerland until Mai 2008. Up to June 2006 me and the Autonomous System Lab were located at Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. \n\nBefore joining the Autonomous Systems Lab I studied Computer Science at the Universities of Dortmund and Stuttgart (both Germany) where I graduated in 2003 with my master thesis about a collision avoidance system for heavy-duty vehicles. \n\nMy main research interests are in the field of autonomous driving and driver assistant systems. 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To achieve this, developed sensors are used to collect data from connected smart objects in the physical world. The gathered data are then uploaded into the cloud and become big data. These data are then integrated and utilized for the development of intelligent systems. Therefore, the IoT is one of the core technologies that is driving the Fourth Industrial Revolution. Moreover, intelligent systems are continually being developed to process big data through the IoT. One of the special characteristics of these intelligent processing-based services and products is the capacity for customization and personalization. Consequently, new and potent values can now be created in smart systems using smart technologies, including the IoT, for a dynamic smart world.
\nIn the early 2000s, during the advent of the IoT, radio frequency identification (RFID) technology was developed for logistic and inventory management applications. It was mainly applied to reduce product distribution and factory production costs. It was also utilized to trace the locations of products being delivered using location-based information systems. RFID technology then continuously evolved and developed into machine-to-machine (M2M) applications, which enable direct communications, monitoring, and controls between devices with a remote application infrastructure using communication channels. More recent M2M communication has expanded into the Internet. Specifically, utilizing wired or wireless communication channels between IP networks, it transmits data between humans and things and between things and other things, such as between household appliances. The Internet itself has also evolved into the IoT as the third generation of the Internet. The first generation of the Internet was developed to be enterprise oriented as the Internet of Computers (IoC), and the second generation of the Internet focused on customers as the Internet of People (IoP) [1]. Eventually, the internet of things (IoT) became an advanced form of M2M.
\nIn 1999, the term “the Internet of Things” was first coined by Kevin Ashton [2]. Initially, the term referred to a type of computer network that can gather a lot, and a wide variety, of data from all of the physical things in the offline world. In order to obtain these data, these things have embedded sensors that record data and transmit them through connections to the Internet using IP networks. According to Kevin Ashton [2], the unique importance of the IoT comprises the following factors. First, the IoT was introduced as a new and powerful method to gather information that was not possible to be gathered in the past. From these tremendous amounts of collected data, the IoT enables the discovery of an almost infinite amount of previously inaccessible facts. Consequently, many manufacturing companies are now attempting to transform themselves from manufacturing to service-based companies, such as the General Electric (GE) Company. Predix is GE’s cloud-based platform (PaaS) for industrial Internet applications that combine people, machines, big data, and analytics [3]. Applications of IoT technology are manifold and diverse. For example, government organizations can use discovered data extracted from the IoT to discover and prevent terrorist attacks. It is also easy to extend IoT-based systems due to good scalability and flexibility. In fact, IoT-based systems can be extended as much as the Internet itself has been extended. For example, new services that are based on IoT applications, such as IoT-based new car-sharing services or parking lot searching services, can be added to previously built systems, leading to the possibility of an infinite extension of the services. Indeed, with relatively little effort, systems and services can be expanded to create new and massively powerful values and opportunities. It is anticipated that the world will witness exponential expansion of diverse applications of the IoT in the near future.
\nUsing big data collected, processed, and integrated through the IoT, intelligent systems have been developed to connect intelligent things. The IoT is thus closely related to intelligent systems because its development is based on the enormous amount of collected data. Generated data in the online and offline world can be propagated and shared in real time by anyone who needs or wants it. They can be also used and analyzed to provide products or services in business and public sectors. Using the IoT, it is possible to collect personalized data, such as at what time someone came to a physical location, in what he or she is interested in, and how long he or she remained in that place. After data analysis, customized and personalized services can be generated that are dynamically developed depending on users’ analyzed characteristics, as well as requirements. To analyze data and generate a relevant service, it is also necessary to utilize intelligent applications and systems. For instance, Amazon’s Dash Button device uses Wi-Fi and Bluetooth technology. It is enabled by a mobile phone, collects personalized data, and provides a corresponding customized service. To do this, the Button technology must be connected to the IoT, intelligent systems, big data, cloud, etc. It processes different contents each time that the button is pushed through the use of smartphone apps to send and receive information. In this way, it provides valuable customized content. In this system, big data technology is also requisite because data are accumulated each time that the button is pushed. By using this button system, it is possible to connect the online to the offline world by gathering so much data from the offline world. Therefore, the IoT is clearly different from previously developed electronics and technologies because it can create new opportunities, services, businesses, and platforms by connections and communications with the online to the offline world.
\nThis chapter is organized as follows. In Section 2, we introduce the global growth of the IoT, trends in the global markets, and current and potential uses of the IoT in government and business sectors. Section 3 introduces sensors, networks, and service interfaces of IoT-based technologies and created services. In Section 4, we discuss IoT-based service applications, such as smart workplaces, smart factories, smart healthcare systems, etc., as well as an example of a smart city application and potential hazards of the IoT. Finally, we present some conclusions.
\nIn the global market, a variety of expectations exist regarding the internet of things (IoT). These expectations are related to how IoT devices will be connected, what are the services and values that will be created, how it can be used to increase a company’s market share, etc. Although forecasts may vary slightly regarding the ubiquity of the IoT, it is obvious that it is growing dramatically. This rapid growth is attributable to the creation of new service markets, the expansion of the IoT devices, and the ease with which the IoT can be applied to industry, governments, products, and services. It is also clear that the growth of the service market, in particular, will comprise a major portion of the IoT market.
\nConcerning this IoT device market, Gartner predicts that, by 2020, the number of connected things will reach 25 billion and the service market will grow to USD $ 300 billion by the same year [4]. In Directions 2016 [5], the IDC forecasts that the number of terminals connected to the Internet will reach approximately 80 billion units in 2025. In addition, Cisco expects that, by 2030, there will be over 37 billion Internet units, the number of IoT devices will reach 50 billion, and the IoT will develop into the Internet of Everything (IoE) [6]. Gartner also predicts that China, North America, and Western Europe will be most active in adopting IoT devices, which will account for 67% of all Internet devices in 2017 [1].
\nIn addition, the service market is also expected to occupy a large proportion of the IoT market. According to Gartner, in 2020, more than half of all existing Internet devices will connect with regular customers. Moreover, the number of customers using home automation systems and entertainment information will amount to 13 billion [7]. Cisco also predicts that 250 million people will be connected to the Internet by 2020. According to IDC, the expected IoT market will be USD $ 1.46 trillion by that same year [8]. These forecasts are based on the development of IoT-related products and the increase of related software and applications. Business and labor markets associated with data centers and management infrastructures will also be expanded to manage increasing data traffic. The consumer segment is predicted to comprise 5.2 billion units, accounting for 63% of the total installed capacity, leading to the ubiquitous use of IoT devices. Moreover, the business sector is anticipated to reach 3.1 billion connected units by 2017 [9]. To leverage the IoT, Mckinsey [10] defined nine key relevant environments: factories, cities, healthcare, retail stores, workplaces, logistics, transportation, housing, and offices. Economic effects range from USD $ 3.9 trillion to USD $ 11.1 trillion, depending on the availability of the IoT [10]. Machina Research (2015) predicts that the global market for the IoT will reach USD $ 1.2 trillion by 2022 [11]. In 2013, the market was USD $ 200 billion, but Machina Research forecasts that the market will grow 22% annually [11]. In addition, market size is expected to increase in the order of terminal, platform, and service by 2022. The average annual growth rate of service and platforms from 2013 to 2022 is expected to be 90.0 and 66.1%, respectively.
\nIt should be noted that the growth of the service market is intimately related to semiconductor chipsets, communication modules, terminals, platforms including systems and solutions, and communication and service applications for device markets that support the IoT. From 2013 to 2022, each of these markets is forecast to have 19.2, 18.7, 8.8, 66.1, 17.0, and 90.0% of the compound average annual growth rate (CAGR). Global consulting firms, Gartner and IDC, forecast that the global IoT market will grow at a CAGR of 31.4 and 17.5% in 2013 and 2020, respectively. According to Cisco, the market value created by IoT corporations is expected to be USD $ 14.4 trillion over the next 10 years, and the public sector will be approximately USD $ 4.6 trillion. IDC expects that the IoT market will increase from approximately USD $ 2 trillion in 2013 to USD $ 7 trillion in 2020. Demands related to software applications, services, and devices for the IoT will also continue to increase. Consequently, in accordance with this demand, service markets from smart factories, smart healthcare systems, connected services, etc. [12] will also grow.
\nCurrently, in order to realize economic and social innovations, governments and public sectors are also focusing on the internet of things (IoT) as a means of announcing policies that they want to promote. Through this, national governments around the world are rapidly establishing public goals, such as strengthening national competitiveness, improving people’s quality of life, and taking actions that will catalyze major economic development. Certain large countries, based on developed information and communications technology (ICT), are strongly supporting the development of the IoT as a national project, including the USA, Japan, China, Europe, and South Korea. China, for example, established the Sensor Network Information Center in 2009 and the Intelligent Things Communications Center in 2010. Through these two institutions and others, China is announcing, establishing, and promoting various national projects. One of them is the “12-5 Plan for Development of the IoT” as part of the twelfth 5-year plan from 2011 to 2015 in 2011. It is building IoT pilot complexes targeted at facilitating the use of the IoT and the cloud as strategic measures [13]. The EU has also announced an implementation plan, including the 2009 IoT Detailed Treatment Plan. The UK is increasing IoT development funds and has announced that it is planning to invest $ 100 billion in the development of IoT technology by 2025. In 2008, the USA focused on building a hyper-connected network infrastructure to extend its existing communication infrastructure to the IoT. In early 2000, Japan accelerated national projects related to the IoT. In 2013, Japan implemented major ICT strategies, such as building smart towns, smart grids, and remote monitoring capabilities. In 2013, South Korea announced a comprehensive IoT plan for the development of technology and related market creation.
\nMany large global companies are actively participating in technology development and building ecosystems of technology focused on the internet of things (IoT) market. For example, Google has announced an ambitious plan to include the smartphone operating system “Android” on all major devices, such as televisions, automobiles, and watches. The company is also continuing strategic mergers and acquisitions (M&As) with related companies, e.g., the Nest company, which provides control services for room temperature, and Dropcam, an Internet surveillance camera manufacturer. Cisco has also led the IoT platform with IOx as an environment for the execution of IoT applications. In addition, Cisco recently announced that it had acquired Tail-f Systems, as a provider of network management solutions, and will acquire Assemblage, a real-time collaboration solution provider. Cisco, as the global market leader in networking equipment, has built an “Interloud” for the entire Internet of Everything (IoE) and is actively pursuing the IoT business through its “Smart Connected Communities” project. In addition, Qualcomm leads the open-source object Internet framework to connect devices with AllJoyn. General Electric (GE), as a leading equipment manufacturer, has announced that it will create new value with the “Industrial Internet Consortium” in connection with the IoT. In GE, the adopted IoT is available to provide new types of services or events. For example, GE’s Predix collects data to monitor factories or systems, estimate possible faults during factory or system operations, and provide appropriate solutions for these faults [3]. AT&T is also working with Cisco, GE, IBM, Intel, and IoT network providers that connect all devices [12]. In recent years, M&As have also been increasing in global IT companies, such as Cisco and Google. This has been identified as a major activity that is preparing for the dominance of the IoT era. Therefore, it is important to ensure competitiveness in each service industry, including distribution, healthcare, security, and finance. It is also essential to possess the capabilities of an IoT value chain, such as content, platform, networks, and devices. For example, platform vendors, such as Microsoft and Oracle, are working to take advantage of their platforms, Microsoft Azure (Azure) and Java ME (Java Platform, Micro Edition), respectively, to prepare for a strong position in the IoT platform market. Moreover, Qualcomm, Intel, and other chipset vendors have focused their devices on the IoT network through AllJoyn and Quark. They are specifically focused on wearable devices and smart homes in the IoT market [12].
\nSensors play a critical role in the internet of things (IoT). Sensors collect data on the Internet by smart devices, which are then used to upload information to the cloud. To achieve this, sensors are embedded in physical devices or exist in the form of external devices. Sensing technology is utilized to acquire a broad range of information, such as position, motion, images, etc. They can also collect surrounding environmental data, including temperature, humidity, heat, atmosphere composition, light, and sound. The IoT is also used to remotely control air conditioning, heating, and lighting. It is important to note that many physical sensors are also evolving into smart sensors with built-in standard interfaces for improving information-processing capabilities and applicable functions. Sensors can also include virtual sensing functions that extract specific information from the sensed and accumulated data. Moreover, virtual sensing technology can be implemented in the actual IoT service interface. Using multidisciplinary sensor technology, which is one-dimensional higher than existing independent sensors, it is also possible to extract more intelligent and high-dimensional information.
\nFor the connection of sensors, the network interface plays the role of connecting physical network devices. For wired and wireless IoT networks, physical devices include wireless personal area networks (WPAN), Wi-Fi, 3G, 4G, LTE, Bluetooth, Ethernet, broadband convergence network (BcN), satellite communication, microwaves, serial communication, and PLC. These and other advanced communications systems enable the possibility for people, things, and services to become closely and rapidly connected.
\nThe devices, such as sensors and network modules, are fixed on terminal devices for the collection of data. In other words, the development of sensor technology is essential to collect and extract data from objects. In addition, it is obviously necessary for network modules to communicate with these sensors, constituting an interworking of Internet communication, an application system, and an embedded system for providing user interfaces (UI). For activating the IoT, optimization and evolution of network technology are very important. The IoT can be connected to a network in a variety of ways. For example, things can be directly connected to a wireless network or connected to a smartphone through communication systems, such as Bluetooth. In the case of non-portable products, it can be connected to a protocol such as Wi-Fi, which is fixed in a certain place, such as a smart home or Industry 4.0.
\nIt is important to note that the IoT service interface differs from traditional network interfaces. The primary aim of the IoT service interface is to offer value-added services through transformation, processing, extraction, and accumulation of sensed data. Additionally, it must make it possible to judge, contextualize, recognize, protect privacy, ensure security, authenticate, allow, discover, shape, etc., for the creation of services. The IoT service interface interlocks three major components: people, things, and services. For the application services to perform specific functions, the IoT must provide some interfaces for accumulating, processing, and transforming data for services, such as ontology-based semantics, open-sensor APIs, augmentation, virtualization, location identification, process management, open platform technology, etc.
\nThe new types of value chains can be created based on the sensor devices, networks, and services in the IoT environment. This means that it can create new types of services that are based on different types of value chains on a data platform that is based on the particular device’s sensing technology. The IoT contributes greatly to the derivation and creation of services based on connections between devices, things, and people. Ultimately, the created services, operations, and products will be based on convergence between data and services using data collected through sensors.
\nThe processed data can also be accumulated in a cloud computing environment as big data. It is obviously critical to integrate data collected from distributed things through the IoT for the creation of advanced services. To achieve this, a data platform that can integrate distributed, collected, and aggregated data is requisite. This platform enables the creation of services that can generate value from different types of data. Service applications on such a data platform are introduced in the next section.
\nThe internet of things (IoT) is expanding the service market that is focused on public safety and distribution through merging with various industries. It is anticipated to be expanded to intelligent transportation services; social infrastructure, such as buildings and bridges; remote management services, existing healthcare, and smart energy-related fields. If the IoT becomes firmly established, its influence is expected to include everyday life, as well as all industries, due to the development and increased use of certain technologies, such as wireless networks, communication modules, sensors, and smart terminals. Furthermore, medical, transportation, manufacturing, distribution, education, and other fields will bring significant changes to existing processes and services.
\nThe smart workplace constitutes a new paradigm for working that will greatly increase collaboration, communication, and intelligent decision-making. It is based on connected, knowledge-based, integrated, and intelligent work facilities that depend on the new technology platform. One of the core technologies involved in creating smart work places is the IoT [7, 14]. Software applications that will be supported by the IoT have also been developed to support smart workplace environments, such as videoconferencing, new knowledge-sharing capabilities, and tracking the location of key mobile business assets.
\nThe smart factory is not the automation-based factory system that existed in the Third Industrial Revolution, but is rather an intelligent system to support customization according to customers’ requirements. This results in greatly increased production efficiency, more accurate and less expensive inventory systems, etc. Smart factories are developed by intelligent systems that are based on collected data from intelligent devices, integration of the collected data for the creation of services, and uploading the data to the cloud. In factories, it is important to interconnect facilities, such as overall systems, processes, and machines, in order to enable advanced services, such as innovation of production processes and cost reduction in supply chains. The IoT has also assumed a role in monitoring and maintaining infrastructure in smart factories.
\nFor smart health, hospital information systems usually use the internet of things (IoT) to monitor and connect patients, doctors, medical devices, and application systems, such as X-rays, using sensors. Some healthcare systems, such as IBM Watson, possess partnerships between people and systems. For example, instead of always requiring the presence of a medical doctor, in some cases, IBM Watson can treat patients by itself because it possesses expert knowledge and constitutes an intelligent system. In this type of case, the IoT is used to track, collect, and integrate remote data and the location of mobile assets in order to create and provide intelligent and advanced medical services. It is also applied to greatly increase the efficiency of healthcare infrastructure and resource usage. It is important to note that the developed applications can also substantially increase profits. Consequently, the more resources that can be saved, the greater the likelihood that new services will be developed. In fact, eight out of ten healthcare leaders (80%) stated that innovation has expanded since the advent of IoT use [7, 14].
\nNearly half of retailers worldwide allow network access on individual mobile devices to build the internet of things (IoT). This can create many new experiences and services for customers. For example, such applications of the IoT use a store’s location service to provide customized information about products. It also assists in obtaining and retaining customers due to customization systems based on collected, accumulated, and processed data concerning individual customers. Currently, the retailing process is changing from a supplier-based value chain to a value-added value chain that is based on customer-centric services. Through the IoT, it is now possible to collect customers’ personalized information, and the accumulated data can be applied to develop new types of services that can be based on intelligent systems. Since the IoT can facilitate more beneficial and customized services for individual customers, developing such services is currently very popular.
\nRecently, with smart farms, many countries and farmers are actively attempting to utilize the Internet, nano-based devices, and robot technology. In 2014, the National Weather Service and the Department of Agriculture established an open data policy and developed various smart agricultural services [15]. For example, Fujitsu grows hydroponic lettuce using its Internet technology platform (Akisai) and is developing it as a new type of farm. In agriculture, food seeds, seedlings, and information about them can be sent directly to consumers, allowing people to grow agricultural products themselves at home. Of course, commercial farmers can also use such services supported by the information provided by the IoT. In addition, by using the IoT, it is now possible to remotely monitor and control conditions for crops and farms. It can monitor and control essential factors, such as humidity, sunshine, temperature, etc.
\nUnlike in the past, automobiles can be now viewed as a digital mobile software system and not as a machine with an engine. Accordingly, such modern cars are often termed “connected cars.” In fact, advanced cars have more than 100 million lines of source code, which supports autonomous operation, self-parking, control, infotainment, safety, performance monitoring with built-in sensors, and inter-vehicle communication. Gartner predicts that, by 2020, connected cars will deliver a new in-vehicle maintenance service and autonomous navigation capability. It is further expected that there will be more than 250 million such units, and one out of five vehicles globally will be connected to a wireless network through the internet of things (IoT) [16]. This rapid increase in vehicle connectivity will affect the overall functionality of telematics, autonomous navigation, infotainment, as well as mobile services, such as mobile banking and remote offices. Over the next 5 years, the proportion of new vehicles with these features is anticipated to increase at a truly dramatic rate, and connected cars will constitute a major part of the IoT [17].
\nHall [18] defines a smart city as a city that “monitors and integrates conditions of all of its critical infrastructures, including roads, bridges, tunnels, rails, subways, airports, seaports, communications, water, power, even major buildings, can better optimize its resources, plan its preventive maintenance activities, and monitor security aspects while maximizing services to its citizens.” According to Harrison et al. [19], the smart city is defined by “connecting the physical infrastructure, the IT infrastructure, the social infrastructure, and the business infrastructure to leverage the collective intelligence of the city.” Recently, the definition of the smart city has been expanded to include not only physical aspects, such as city infrastructure, but also concepts that comprise nonphysical factors, such as the environment and governance. The United Nations Conference on Trade and Development (UNCTAD) [20] defines the smart city as smart mobility, smart economy, smart living, smart governance, smart people, and smart environment. Data for smart cities originate from all infrastructure and things in the city based on internet of things (IoT) technology. Services are then developed to enable citizens to have greatly expanded and personalized options in their lives by using the collected data. The IoT overall was developed for the purposes of connecting various things to exchange information and realize value-added information services. Consequently, if the IoT is intelligently applied to cities’ facilities, management, and security, city functions could be performed much faster and more efficiently than was previously the case. If a hyper-connected society that connects things and cities becomes a reality in the near future, we will experience truly smart cities that can integrate city management systems that were previously operated individually.
\nAs progress has been made in IoT uses and applications, public sectors are linking building security systems (57%), street lighting (32%), and automobiles (20%) to create an organic technological environment that will support the smart city of the future. The most widely deployed IoT applications in this sector comprises remote monitoring and control of urban devices (27% responded that this is the main application) and constitutes an essential step toward actualizing the smart city’s integrated infrastructure.
\nPaul Manwaring [21], cofounder of the IoT Living Laboratory in Amsterdam, stated that “we need to empower communities to solve their own problems.” Certainly, problems still exist that need to be solved to achieve sustainable development. These problems are mainly due to industrialization activities that are based on digital technology.
\nThe internet of things (IoT) has been identified as a core technology for building smart cities. Therefore, many countries around the world are promoting smart cities to obtain various benefits. As one of the efforts to solve the abovementioned problems, we focus now on trash cans equipped with IoT sensors to assess load quantity in real time. In early 2016, 76 IoT sensors were attached to trash cans in major commercial districts in Seoul, Korea. In June 2017, Goyang city built a smart collection management system based on the IoT [22] as the IoT demonstration complex. The IoT sensors are installed in the trash cans in various locations along city streets and in resident public trash cans to manage loads in real time. A load detection sensor, a solar compression device, and a garbage collection tracker and system are installed in the trash cans. The IoT trash can with the load-sensing control is equipped with a sensor inside of the trash can’s lid to measure the load in the trash can in real time, and the compression trash can is automatically compressed to prevent trash can overflow when too much garbage accumulates. In addition, the sensor is powered by solar energy. In garbage collection vehicles, a tracker is installed, and the vehicle position and collection routes are displayed in real time. The amount of garbage collected by each vehicle in the landfill can also be quantified and systematically managed. The measured data in the smart trash can are transmitted to the Goyang city demonstration center server and to environment-friendly smartphones. Finally, garbage-loading information can be checked and managed in real time. This is an example of using the IoT to successfully solve a generally occurring problem in most cities.
\nIt is certain that the internet of things (IoT) will provide tremendous opportunities in manifold regions and industries. However, a fundamental gap still exists between understanding and preparing for the anticipated ubiquity of the IoT. For example, although 98% of organizations that have adopted the IoT claim to be able to analyze data, almost all respondents (97%) stated that it is still difficult to generate value from these data. In fact, more than one-third of companies are not extracting and analyzing corporate network data and using these insights to improve business decisions. One of the biggest limitations is security of data and information to protect IoT-based systems from external threats.
\nIn this chapter, we introduced the internet of things (IoT), which is a new type of a network that connects device to device, device to people, device to place, etc. The network communications are based on an Internet protocol (IP), such as that used for the Internet. The communications are conducted using embedding or external sensors in devices or objects. Through these communications, tremendous amounts of data are generated. These data are termed big data and are uploaded to a cloud system. This enormous amount of data can then be utilized to create valuable new services and products. In addition, through using the accumulated data, some systems and markets provide powerful intelligent services and applications, such as smart workplaces, smart factories, etc.
\nWe are already living in a hyper-connected world where people and intangible things are networked through the IoT. Indeed, the IoT is leading the era of superfusion that is creating multifaceted economic, social, and ethical values that converge with various industries and expressed as productive business models. In the era of the IoT, most devices use gathered information and network connectivity that actively exploit collected data through a variety of sensors to drive opportunities for new products and services. From this perspective, the IoT integrates intelligent networks which can be systematically linked with humans, things, and services for distributed sensing, networking, and processing.
\nAs one of the IoT applications, the smart city was introduced in this chapter. The smart city can be understood as a kind of hyper-connected world comprising the overall society, business platforms, the environment, etc., with newly developed technologies, such as big data, cloud, and artificial intelligence. Smart cities can also embed these applications and innovations, such as in connected vehicles, smart homes, etc.
\nInitially, the IoT was developed for simple communications between devices and objects through RFID and M2M technology. However, the IoT is creating a new type of hyper-connected world that comprises connected societies, connected environments, etc. It also creates entirely new types of services, products, and businesses that were not even envisioned in the past. For example, when the Internet first appeared, it was not expected that it would revolutionize the world, but it did. This time, the IoT is changing the world and to no less of an extent.
\nIn near the future, in our hyper-connected world, we will be able to experience a truly smart world which integrates systems that were previously operated individually and create powerful new values and opportunities that we have never experienced.
\nDrug delivery refers to the approaches or methods or technologies of administering or transporting active pharmaceutical ingredient(s) and other xenobiotics through different routes for achieving the desired therapeutic effect in human or animal safely. The pharmacokinetics and pharmacodynamics issues of drugs are the most important considerations of drug delivery which is profoundly integrated with dosage form and route of administration. The kinetics of drug release, drug concentration profile in the plasma, onset of action, duration of action, site of action, and side effects of a drug deeply influenced by the DDS.
\nConventional drug delivery system is also known as classical drug delivery system or traditional drug delivery system, which sometimes unable to maintain the steady-state plasma concentration as desired for a specific time period and may not be able to deliver the drugs to the specific site of organ or tissues may be because of barriers in transportation for which it may be needed to administer with multiple doses at a regular time interval or need to go for targeted drug delivery systems.
\nTargeted drug delivery system (TDDS) is popularly known as smart drug delivery system. The aim of the TDDS is to localize, target and to have a protected interaction of a drug with the diseased cells/tissues of interest for a prolonged period of time. TDDS helps in maintaining the requisite plasma and tissue drug levels in the body and protects the healthy tissues from damage may be some times caused by the drugs [1]. It offers various benefits over conventional DDS such as localization of a drug to the desired or specific site, enhancement of therapeutic efficacy, reduction in the dosing frequency and toxic side effects, controlled biodistribution of drug, modulated pharmacokinetics, and improved patient compliances [2]. The TDDS is a highly integrated DDS which needs the coordinated effort from various experts such as biologist, chemist, engineers for its fabrication and optimization.
\nNanotechnology is defined as the technology which allows studying, controlling, manipulating and manufacturing of structures or devices in the nanoscale. It is a multi-disciplinary scientific field applying engineering and manufacturing principles at the molecular level. These nanosized objects/structures/devices, e.g. “nanoparticles” exhibit unique properties and function that distinctly differ from those seen from the items made up from the same materials. Nanomaterials possess many unique characteristics such as mechanical, optical, magnetic, electrical, and biochemical, which provoke them to intermingle with complex cellular functions in an exceptional manner [3].
\nSince its introduction in 1959, the nanotechnology brought a great revolution in all areas of sciences and particularly in drug formulation and drug delivery system design. Nanomedicine is the medical application of nanotechnology, which plays an imperative role in the medical biology, diagnosis, monitoring, prevention and treatment of diseases. Since last few decades, owing to the rapid developments in nanotechnology and carrier materials, a great advancement in the nanoparticulate DDS has been noticed and they are taking the lead among all types of DDS [4].
\nThe nanoparticulate DDS possesses numerous advantages such as higher intracellular uptake (cells and tissues have a greater affinity and acceptability to the nanoparticles as compared to micro/macro molecules), ability to penetrate into sub-mucosal layer (nanometric size), greater suitability for administration through the systemic circulation (nanometric size), greater feasibility/flexibility to develop into a targeted DDS for targeting various sites/organs. Thus, the nanometric size, tailored surface, and cross functionality of these nanoparticles will continue to explore many unexplored research areas and may help in designing and developing new biomedical applications [5].
\nThe term “colloid” is applied to the dispersed system where the dispersed phase particles size are very fine and generally below 1 μm. Thus, the biphasic drug carrier containing very fine dispersed phase particles (<1 μm) which sequester, transport and retain the active drug en route, while they deliver the drug within or in the vicinity of a target is popularly known as colloidal drug carrier. These colloidal drug carriers comprise nanoparticles, liposome, niosome, nanospheres, multiple emulsion, and nanosuspensions, etc. [6]. Colloidal carriers aid in solubilization of lipophilic drug, protect the sensitive drug from degradation in biological fluid, reduce toxic side effect, improve patient compliances, prolong the duration of action and drug targeting potentiality [7].
\nThough the polymeric nanoparticulate DDS have shown hugely impressive performance for providing therapeutic benefits in the case of long term delivery of a therapeutic agent, but still, the number of polymeric nanoparticulate formulations in the market is still limited. This is because of polymeric toxicity, high cost of polymers, and lack of feasibility for scaling up. Lipid based nanoparticulate DDSs are proposed as an alternative to polymeric nanoparticulate DDS and gained tremendous attention in the field of nanomedicine. These comprise liposomes, niosomes, nanoemulsions, solid lipid nanoparticles (SLNs) and nanostructured lipid carrier (NLCs), etc. [5].
\nSLNs are the second generation lipid nanocarriers that overcome most of the limitations associated with conventional drug delivery system and other colloidal lipid/polymeric nano carriers. It promises to offer numerous benefits including biocompatibility and biodegradability, physiochemical stability, lower toxicity, ability to incorporate both hydrophilic and lipophilic drugs, improved bioavailability, enhanced
In the emerging field of nanomedicine, SLNs is at the forefront. It is made up from biocompatible/physiological lipids (e.g. partial glycerides, triglycerides, fatty acids, wax, and steroids) that remain in solid form at room temperature. Numerous techniques are being developed for the fabrication of SLNs using the biocompatible/physiological lipid which has records of innocuous use in medicine [8]. Apart from drugs, the essential materials for fabricating SLNs are solid lipids as matrix materials, emulsifiers, stabilizers, and water. The nanometric size and larger surface area of SLNs is suitable to be embedded with some potential functionalized ligands, antibodies, moieties, and other functional groups that help in drug targeting [5].
\nThe real success of lipid nanoparticles relies on the development of dosage forms that are able to improve the therapeutic index of the drugs by mounting their concentration specifically at the targeted site or organs. Drugs can be incorporated in SLNs which lead to offer a new model in drug delivery that could be applied for drug targeting. The therapeutic payload of various categories of drugs (such as anti-infective, anticancer drugs, anti-inflammatory, etc.), antigens, proteins, and nucleotides can be enhanced in specific site and organs by associating with SLNs. On another side, SLNs face numerous challenges which include rapid clearance, serum instability (dependent on the specific formulation) and nonspecific uptake by the mononuclear phagocytic system (play a major role for opsonizing the foreign particles and remove SLNs from the circulation) [9]. The above mentioned limitations can be nullified by conjugating different ligands to the surface of SLNs which could help to increase the circulation time and targeted delivery of the drug to the specific site. The targeting properties to a specific site can be further enhanced by selecting surface markers [10]. Thus, in this article, we focused on SLNs and various ligand conjugated SLNs which act as suitable carriers for targeting to different sites such as lungs, brain, liver, breast, eyes, colon, kidney, etc.
\nTargeted delivery of a drug to the lungs is gaining much more interest at the present time, for the treatment of lungs cancer, tuberculosis, and other airborne diseases where lungs are the primary site of action or site administration of drugs [11]. In order to get maximum therapeutic benefits from lungs delivery, a suitable DDS with appropriate physicochemical properties are necessary and SLN along with ligand conjugated SLN are the most fitted on this ground.
\nThe lungs offer a very high surface area for rapid absorption of drugs owing to high vascularization and avoidance of the first pass effect. Sometimes, targeted delivery of certain drugs to the lungs is very important not only for improving the bioavailability and therapeutic activity but also for reducing the systemic side effects [5].
\nTo achieve a prolonged hypoglycemic effect, Liu et al. developed insulin-loaded nebulized SLNs which were administered through intrapulmonary route. The hypoglycemic effects, stability of SLN during nebulization, and deposition pattern of the drug were evaluated. SLNs exhibited excellent protective effect for insulin against degradation or leakage from nanospheres and were relatively stable during nebulization
Rifampicin (RIF) were successfully encapsulated into the SLNs that delivered RIF specifically to the alveolar macrophage (AM) with strong antimycobacterial efficacy (MIC reduced to 1/8 fold than that of the free drug). Generally, mycobacterium safely multiplies in the AM (acts as an incubator), as the mycobacterium is resistant to the biocidal mechanism of AM. The developed SLNs were more stable and the particle sizes were very much suitable for improving RIF’s uptake by AMs which are particle size dependent [14]. Similarly, Rifabutin loaded SLNs significantly improved uptake of the drug by the macrophages which were demonstrated in an
Co-administration of RIF and isoniazid through SLN formulation significantly reduced (60%) degradation of RIF (from 48.81 to 12.35%) from acidic gastric pH owing to the presence of isoniazid. The developed SLNs promoted targeted delivery of drug to the brain with enhanced bioavailability and lesser side effect that could be helpful in the case of cerebral tuberculosis [16].
\nSignificantly higher biodistribution of dexamethasone acetate (DXM) to the lungs was achieved through intravenous administration of DXM loaded SLNs. The area under curve (AUC) of DXM- SLNs was increased by 17.8-fold as compared to DXM-solution. The maximum concentration of the DXM in the lungs was observed at 0.5 h post DXM-SLNs injection [17].
\nSimilarly higher biodistribution of amikacin (AMK) in the lungs was achieved by pulmonary administration of AMK-SLNs as compared to the free drug administered through i.v., which could be helpful in the treatment of cystic fibrosis [18].
\nLungs targeted delivery of drugs is a challenging task due to the mucociliary clearance. In this regard, the ligand-anchored DDS not only proves its potential in achieving improved site-specific drug delivery, but also it reduces the chances of drug uptake by reticulo-endothelial system (RES). It is believed to play a major role in congenital defense and exhibit diversified biological activities such as antimicrobial, anticancer, immunomodulation, an exertion to control cell growth, binding, and inhibition of numerous biologically active compounds. However, clinical success of such approaches relies on the choice of appropriate ligand free from immunogenic potential with the potential to provoke cargo internalization by the target cell [19].
\nThe mechanism of receptor mediated endocytosis of ligand anchored SLNs and drug release technique has been shown in Figure 1.
\nMechanism of receptor mediated endocytosis of ligand anchored SLNs and drug release technique.
In lung associated diseases, receptors of Lactoferrin (80-kDa iron-binding glycoprotein) is overexpressed in the lungs. Thus, Lf conjugated DDS may become a promising tool for targeted delivery of drugs to lungs in lung-associated diseases [20]. Rifampicin (RIF) loaded SLNs were successfully prepared and were coupled with Lf via carbodiimide chemistry i.e., coupling of the Lf carboxylic group with the stearylamine amine group present on the surface of the previously formed RIF loaded SLNs in the presence of N-ethyl-N-(dimethylaminopropyl)-carbodiimide (EDC). An
Conjugation of bioadhesive ligand molecules with SLNs helps in improving drug absorption/bioavailability by increasing residence time in the GIT and reducing dosing frequency. Lectins (a group of diverse proteins/glycoproteins) are the bioadhesive ligand and have stable structure and receptor binding ability. It offers resistance to enzymatic digestion/degradation, which helps in its
WGA conjugated SLNs loaded with rifampicin (WRSLNs) were successfully developed for lungs specific delivery of rifampicin (RIF). The conjugation of WGA to RIF loaded SLN was carried out by two-steps carbodiimide reaction reported by Ertl et al. with slight modification [23]. Even after conjugation with the SLNs, the WGA retained its bio-recognition activity and sugar-binding specificity [24]. From the
Studies on tuberculosis revealed overexpression of the mannose receptors specifically on alveolar macrophages (AM) surfaces [26]. Keeping it in mind attempts were taken to develop mannosylated SLN to deliver antitubercular drugs targeting to alveolar macrophages which have higher affinity for mannose. Rifabutin loaded mannosylated SLNs were successfully developed. Manosylation was done by ring opening reactions followed by reaction of aldehyde groups of mannose in 0.1 M sodium acetate buffer (pH 4.0) with the amino groups of lipid. This leads to formation of Schiff’s base (–N=CH–), which may then get reduced to secondary amine (–NH–CH2–) and remain in equilibrium with Schiff’s base at basic pH.
Overexpression of mannose receptors in case of lungs cancer was reported by numerous investigators. The mannosylated-distearoyl phosphatidyl-ethanolamine SLNs loaded with paclitaxel (PTX) was developed for lungs targeted delivery of PTX. Manosylation was done by ring opening reaction followed by reaction of an aldehyde group of mannose with the free amine group provided by stearylamine and DSPE in sodium acetate buffer (pH 4.0). The stability testing data indicated that SLNs formulations stored at 4 ± 2°C were more stable than those stored at 27 ± 2°C. It was revealed that mannosylated SLNs deliver significantly higher concentration of drug to the alveolar cell sites and showed improved antiproliferative efficacy as compared to PTX solution and PTX-SLNs [28].
\nThe folate receptors (α- form) are overexpressed on the surface of lung tumor cells. The extents of the overexpression are different in different types of lung tumors (adenocarcinomas—72%, squamous cell carcinomas—51%, small cell carcinoma—25%, and lung metastases—30%) [29]. These receptors allow folate derivatives to bind preferentially that permits intracellular incorporation of folate derivative by endocytosis.
\nFolate-conjugated copolymer of polyethylene glycol (PEG) and N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) SLNs loaded with Paclitaxel (PTX) were successfully developed. The conjugation of folate- conjugated PEG and HTCC to RIF-SLN was carried out by carbodiimide mediated coupling chemistry. Pulmonary administration of the developed F-PEG-HTCC–SLNs selectively delivered the PTX to the lung’s cancer cells with improved penetrability and prolonged lung residence. Moreover, the developed SLN significantly reduced the
List of SLNs and their different ligand conjugated forms for lungs targeting have been summarized in Table 1.
\nSl. no | \nSLN (Type) | \nLipids | \nPreparation method | \nDrugs | \nTarget | \nModel | \nComments | \nRef. | \n
---|---|---|---|---|---|---|---|---|
01 | \nSLN | \nSA, PA | \nReverse micelle-double emulsion | \nInsulin | \nLungs | \nMale SD rats | \nImproved hypoglycemic effect | \n[12] | \n
02 | \nSLN | \nSA, PA | \nModified lipid film hydration method | \nRIF | \nAM | \nSD rats | \nImproved drug uptake by AMs. | \n[14] | \n
03 | \nSLN | \nSL, GTS | \nUltrasonication with high pressure homogenization | \nDXM | \nLungs | \nMice | \nImproved therapeutic efficacy targeting to lungs | \n[17] | \n
04 | \nLf-SLNs | \nSL | \nSolvent injection method | \nRIF | \nLfR | \nAlbino rats | \nTargeted delivery of RIF to Lungs | \n[21] | \n
05 | \nWGA-SLN | \nSA, GMS | \nSingle emulsification followed by solvent evaporation | \nRIF | \nMucin | \nPorcine | \nControlled release of RIF | \n[25] | \n
06 | \nMsy-SLN | \nTSN | \nModified solvent injection method | \nRFB | \nMR | \nJ774 & albino rats | \nAM specific drug delivery. Enhanced therapeutic efficacy. | \n[27] | \n
07 | \nMsy-SLN | \nTSN, DSPE | \nModified solvent injection method | \nPTX | \nMR | \nA549 & Male albino rat | \nAlveolar cell site delivery of drug with enhanced anti-proliferative efficacy. | \n[28] | \n
08 | \nFt-SLN | \nCHO, GS | \nNano precipitation method | \nPTX | \nFR | \nHeLa & M109- HiFR cells | \nProlonged drug residence time, reduced MIC | \n[30] | \n
List of SLNs and their different ligand conjugated forms for lungs cells targeting.
Targeted delivery of drugs to the brain for is gaining much more interest at the present time, not only for the treatment of brain tumor and other neurodegenerative disorders but also for their diagnosis. Brain targeted delivery of drugs is the most challenging task because of the presence of strongest physiological barrier, i.e., blood brain barrier (BBB). It is a highly selective semipermeable membrane barrier constituted by specialized microvascular endothelial cells, basement membrane and glial cells (astrocytes, neurons, and pericytes). As long as the BBB remains integral, the drugs remain ineffective in the brain. Though BBB is a major issue for it, yet it offers scores of opportunities such as presence of numerous transport proteins and specialized receptors [5].
\nConventional approach for the treatment of brain tumor and other brain-related disorders needs a higher dose of the drug that leads to systemic toxicity and substantial adverse effects on CNS and vital normal tissues. However, various researchers have reported SLNs to be a suitable DDS targeting the brain as the SLNs possess numerous unique characteristics, such as improved uptake of SLN by the brain due to lipidic nature, bioacceptability and biodegradability nature, non-toxic, nano sized particles suitable for prolonged circulation time in blood scale up feasibility, absence of burst drug release effect [31]. Thus, SLN could be used as potential as well as promising candidate for brain targeting.
\nSLNs are the most acceptable brain targeted DDS employed in brain tumor owing to their ability to escape and/or inhibit P-glycoprotein in the blood–brain barrier [32]. Camptothecin (CMP) loaded SLN were successfully developed for the treatment of glioma. Encapsulation of drug in phospholipids and conjugation with the peptide enhances the permeation of drug across BBB, which leads to brain targeted delivery of the drug. The developed SLN was stable in terms of size and charge within a year of storage which might be due to appropriated acidic pH (inclusion of behenic acid into the lipid core of the SLNs). DMPC (1,2-dimyristoyl-sn-glycero-3-phospho-choline) membrane helps in efficient release of the incorporated CMP into the brain parenchyma crossing the BBB. Against glioma, the developed SLNs showed higher cell death or antitumor activity using the lowest maximal inhibitory concentration (IC50) values. Biodistribution study revealed higher accumulation of CMP in the brain in the case of SLNs as compared to other non-encapsulated drugs. However, pharmacokinetics study revealed lower deposition of CMP in peripheral organs indicating lesser toxicological effects in the vital organ. Thus, in short, the SLNs exhibited enhanced accumulation, distribution, and retention of camptothecin in the animal brain along with superior
Riluzole (RLZ), a potent neuroprotective agent is useful in the treatment of neurodegeneration including traumatic brain injury and amyotrophic lateral sclerosis. RLZ-SLNs were able to deliver the riluzole successfully to the brain which helps in preventing acute cell damage induced by glutamate in neurodegenerative diseases of motor neurons. Moreover, it also protects dopamine neuron in the case of Parkinson’s disease. Stability studies on RLZ-SLNs were also carried out at pH 1.1, 5.5 and 7.4, and in human plasma which revealed the absence of riluzole degradation in all the investigated media [34].
\nVinpocetine (VIN), a derivative of vincamine alkaloid, useful against chronic cerebral vascular ischemia. VIN loaded SLN were successfully developed and achieved the objectives of delivering the drugs to the brain. Release kinetics of the developed SLN followed zero-order sustained release profile [35].
\nAugmentation of drug uptake into the brain is a subtle mission in the treatment of brain tumor. Lactoferrin (Lf) receptor present on the BBB in different species along with the cell surface of glioblastomas [36]. Keeping it in mind, various researchers tried to target lactoferrin receptor through conjugation of lactoferrin with SLNs for active targeting to brain tumor. Moreover, this conjugated system showed higher stability, and drug payload.
\nLactoferrin (Lf) conjugated SLNs loaded with docetaxel (DTX) were able to show effective brain targeting efficiency. Carbodiimide chemistry was employed for conjugation of Lf on SLN surface (Lf-SLN). Receptor saturation studies and distribution studies of lipidic nanoparticles in the brain indicated brain targeting mechanism for uptake in brain tumor cell and brain respectively. The Lf-SLNs were more stable. It not only showed significantly higher DTX concentration in the brain but also showed superior apoptotic activity when compared with unconjugated SLNs and DTX. Thus it was confirmed that conjugation of Lf to SLN significantly improved the targeting potential of the DTX for brain tumor [37].
\nP-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRAPs) are localized on brain microvascular endothelial cells (BMEC) which pump out the substances/drug out from the central nervous system. Tamoxifen (Tf), a selective estrogen receptor modulator possibly reverse the capability of efflux transporters like MRAPs in cancer cells [38]. Thus, incorporation of Tf could help in preventing a wide range of medication from efflux loss. Lactoferrin (Lf) receptors are overexpressed in BMEC and glioblastoma multiforme (GBM) cells. It is reported that the Lf cause inhibition to the multiplication of malignant GBM cells.
\nTamoxifen (Tx) and lactoferrin (Lf) cross-conjugated carmustine (CRM)-loaded SLNs were developed. For conjugation of Tx on CRM-SLN, the carbonyl groups of the SLN were first activated with 0.1% (w/v) carbodiimide and 0.05% (w/v) N-hydroxysuccinimide. The suspended SLNs were then crosslinked with 0.05%, 0.1%, 0.15%, or 0.2% (w/v) Tx at 150 rpm and 25°C for 3 h and centrifuged. Further Lf conjugation was done by reacting Lf (0.02%, 0.04%, 0.06%, or 0.08%) (w/v) with the activated CRM-SLNs and Tx-CRM-SLN. The conjugated SLNs were more stable which could be due to inclusion of behenic acid into the lipid core. These were efficiently penetrated through a monolayer of human BMEC and human astrocytes and to target GBM cells. A 10-fold increase in the permeability of BBB and improved the sustained release of CRM was achieved with the help of the developed SLNs as compared to unconjugated CRM-SLNs. Thus, TX and Lf cross-conjugated SLNs enhance the BBB permeability of the drug with improved anti-proliferative action against GBM [39].
\nTreatment of brain tumor through siRNA is preferable, as it can target specifically to one gene and is able to silence it in a post-transcriptional way. Moreover, siRNA can target several functional proteins available at the BBB [40]. Treatment of brain tumor through siRNA, needs a safe, stable, effective carrier which must be able to cross the BBB. The SLNs are mostly preferred as it meets most of the criteria which siRNA needs. Targeted delivery of gene by SLNs is a bi-stage system. Conjugation of angiopep to SLN surface for targeting the low-density lipoprotein receptor-related protein-1(expressed in BBB) is the initial step. The proteolytic cleavage of PEGylated lipopeptide, which releases PEG, glutamic acid residues and release of siRNA for high silencing efficiency is the second stage [5].
\nsiRNA encapsulated SLNs were successfully developed using a combination of titrable cationic lipids. For effective gene delivery, it was PEGylated after incorporating MMP-cleavable lipopeptide. The
Low density lipoprotein (LDL) receptors are overexpressed on the BBB and apolipoprotein E (AP-E), a plasmatic protein is easily recognized by these receptors. Resveratrol (RSV), polyphenolic flavonoid promises to offer neuroprotective effects which are helpful in neurological disorders like Alzheimer’s, Parkinson’s, Huntington’s diseases, brain ischemia, and epilepsy. The AP-E conjugated resveratrol (RSV) SLNs were successfully developed. The binding of ApoE to the SLNs surface was carried out by spontaneous interaction between the previously biotinylated ApoE and the covalently attached avidin on the SLNs surface, resulting in two different ApoE-functionalized SLNs: SLN-DSPE-ApoE and SLN-Palmitate-ApoE. These conjugated SLNs were sufficiently stable and were able to prevail over the issues of RSV like low solubility, degradation but also to help its brain targeted delivery. Brain targeted delivery of RSV by such SLNs follows a bi-stage system. The AP-E-RSV-SLNs mimic lipoprotein particles that are endocytosed into the BBB endothelium via the LDL receptor and then transcytosed to the brain [42].
\nList of SLNs and their different ligand conjugated forms for brain cell targeting have been summarized in Table 2.
\nSl. no | \nSLN (Type) | \nLipid (s) | \nPreparation method | \nDrugs | \nTarget | \nModel | \nComments | \nRef. | \n
---|---|---|---|---|---|---|---|---|
01 | \nSLN | \nCP, DMPC | \nHigh shear homogenization and ultrasonication techniques | \nCMP | \nBrain | \nHuman glioma & Monocytic cell line. Wistar rats | \nEnhanced accumulation of CMP. Superior | \n[33] | \n
02 | \nSLN | \nCOMP, SPC | \nWarm oil-in-water microemulsion technique | \nRLZ | \nBrain | \nMale SD rats | \nHigher bioaccumulation of RLZ in brain. | \n[34] | \n
03 | \nSLN | \nSA, GMS, PRE, GTP | \nHigh shear homogenization and ultrasonication techniques | \nVIN | \nBrain | \n— | \nZero-order sustained drug release kinetics | \n[35] | \n
04 | \nLf-SLN | \nGMS, SA, SL | \nEmulsification and solvent evaporation method | \nDTX | \nLf Receptors | \nU-87 MG cell lines & Swiss albino mice | \nImproved the brain targeting potential | \n[37] | \n
05 | \nTf-Lf-SLNs | \nTPM, DSPE | \nHomogenization followed by centrifugation | \nCRM | \nTf and Lf Receptors | \nU87MG, HBMECs | \nHigher BBB permeability. Superior anti-proliferative action | \n[39] | \n
06 | \nSLN | \nPOPC, DSPE, CHO, DM | \nDetergent dialysis technique | \nsiRNA | \nAngiopep | \nbEnd.3 cell, U87MG cells, | \nHigher uptake and gene knockdown efficacy | \n[41] | \n
07 | \nAP-E -SLNs | \nCP | \nHigh shear homogenization followed by sonication technique | \nRSV | \nLDL Receptor | \nhCMEC/D3 Cell line | \nBrain targeted delivery of RSV | \n[42] | \n
List of SLNs and their different ligand conjugated forms for brain cell targeting.
Though targeted delivery of a drug to the liver is a challenging task, still, it is an interesting approach in the treatment of various liver disorders. In the treatment of liver disorders, drugs targeting to the liver, face irresistible obstacles from various physiological barriers and processes like uptake by the reticuloendothelial system, mechanical entrapment by the pulmonary vascular bed, and opsonization process [43].
\nNumerous approaches are being proposed to enhance bioaccumulation/biodistribution of drugs to liver and hepatocytes. These approaches include both active targeting as well as passive accumulations of nanoparticulate formulation due to ligand (carbohydrate, peptide, antibodies conjugation) conjugated nanoparticles. Recently, liver targeted deliveries of drugs by the SLNs are gaining much attention in the treatment of various types of liver disorders. Thus, various liver targeting strategies using SLNs are enlightened below.
\nBaicalin (BCL), a natural product obtained from
Berberine (BBR), an active constituent of
Cisplatin (CSPT) is an anti-cancer drug which is used in the treatment of many malignancies including hepatocellular carcinoma, lungs carcinoma, etc. The CSPT loaded SLNs (CSPT-SLNs) were successfully developed and were stable in terms of drug content after storage for 3 months in different temperature and humid conditions.
Sorafenib (SFB), a potent multi-kinase inhibitor possess anti-tumor angiogenesis effect (block vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGFR)) and is preferentially used in the treatment of hepatocellular carcinoma. The SFB loaded SLNs (SFB-SLNs) were developed with an objective of improving bioavailability and reducing adverse effects. The results of the stability test showed that SRF-SLNs remained stable for more than 1 month at room temperature.
Primaquine phosphate (PP) is an antimalarial drug that acts on the primary tissue forms of the Plasmodium which after growth within the liver, initiate the erythrocytic stage. Thus, PP loaded SLNs (PP-SLNs) were developed with an aim to deliver liver schizonticide PP directly to the hepatocytes. Stability of the PP-SLNs in suspension was tested for a period of 3 months in terms of size, poly-dispersity, ζ-potential, and pH. There were no noteworthy changes
The fibrous scars occurring in the liver due to the increased production and deposition of hepatic extracellular matrix (ECM) components are called liver fibrosis reduce the physiological performance of the liver. Hepatitis viral infection is one of the major reasons for liver fibrosis and cirrhosis. Administration of antifibrotic therapeutics (e.g. connective tissue growth factor (siRNA) responsible for the cellular and molecular basis of fibrogenesis) is one of the most preferable approaches for the treatment of liver fibrosis. The siRNA loaded cationic SLNs (cSLNs) were developed by gently mixing CSLNs with siRNA at various weight ratios of cSLN to siRNA in 0.1 M PBS (pH 7.4) and then incubated at room temperature for 15 min. Naturally obtained low-density lipids (LDLs) were used in the preparation. The developed cSLN were able to silence the targeted gene in the presence of serum with notably low cytotoxicity. The cSLNs were PEGylated which were hydrodynamically stable and were able to protect their siRNA cargo from nuclease degradation during systemic circulation. The developed cSLNs loaded with siRNA administer through intravenous route delivered siRNA exclusively to the liver and resulted in a considerable reduction in collagen content and pro-fibrogenic factors with spectacular progress of pathophysiological symptoms in a liver fibrosis rat model. Biodistribution study revealed site-specific delivery and accumulation of siRNA loaded cSLNs to the liver tissues [50].
\nPEGylated SLNs are reported to be preferentially accumulated in the liver as the kidney is unable to clear the same. Thus, in liver disorders, liver targeting strategy using PEGylation technique is used for delivering numerous drugs. Paclitaxel (PTX) loaded PEGylated SLNs were successfully developed for targeting the liver, in the case of hepatic carcinoma. The cellular uptake study revealed that PTX loaded PEGylated SLNs showed prolonged circulation time in plasma and higher bioaccumulation of drug in the liver when compared with the PTX solution [51].
\nThe preferential drug targeting ability of PEGylated SLNs to cancer cells have been shown in Figure 2.
\nPEGylated SLN in targeting preferentially to cancer cells.
The parenchymal cells of the liver contain asialoglycoprotein receptors which recognize terminal b-D-galactose or N-acetylgalactosamine residues. The N-hexadecyl lactobionamide (N-HLBA) was synthesized via an amide bond between the amine group of hexadecylamine and the carboxyl group of lactobionic acid. The lactobionic acid was converted to 1,5-lactone that contain more reactive amine groups. Cucurbitacin B (CurB), a tetracyclic triterpene shows significant pharmacological activities including anti-tumor, anti-hepatitis, hepatocurative and hepatoprotective. The CurB loaded N-hexadecyl lactobionamide (N-HLBA) conjugated SLNs were developed for liver-targeted delivery of CurB. The N-HLBA SLN with anchored galactose moiety via amide bonds might achieve effective liver-targeting delivery
List of SLNs and their different ligand conjugated form for liver targeting have been summarized in Table 3.
\nSl. no | \nSLN (Type) | \nLipid(s) | \nPreparation method | \nDrugs | \nTarget | \nModel | \nComments | \nRef. | \n
---|---|---|---|---|---|---|---|---|
01 | \nSLN | \nSL, GMS | \nEmulsification ultrasonic dispersion method | \nBCL | \nLiver | \nRats | \nImproved biodistribution of BCL in Liver, Superior anti oxidative and hydroxyl radical scavenging abilities | \n[44] | \n
02 | \nSLN | \nSA | \nHot-homogenization followed by ultra-sonication | \nFB | \nLiver | \nHepG2 cell line, Rats | \nAnti-oxidant, anti-inflammatory and detoxification potential | \n[45] | \n
03 | \nSLN | \nGL, SP, TP | \nHot Emulsification Technique | \nBBR | \nLiver | \nMale db/db mice, | \nDown regulate the lipogenic gene and Up-regulate the lipolytic gene. | \n[46] | \n
04 | \nSLN | \nSA | \nWarm emulsification followed by sonication | \nCSPT | \nHepatocellular carcinomas | \nWistar rats | \nHigher bioaccumulation of drug in liver | \n[47] | \n
05 | \nSLN | \nGB | \nHigh-speed shearing followed by ultrasonication | \nSFB | \nLiver | \nFemale SD Rats | \nImproved bioavailability, higher bioaccumulation in liver | \n[48] | \n
06 | \nSLN | \nSA | \nModified multiple emulsion solvent evaporation technique | \nPP | \nHepatocytes | \n3D7, Mice | \nImproved antimalarial activity | \n[49] | \n
07 | \nC-SLN | \nCO | \nModified emulsification and solvent evaporation method | \nsiRNA | \nLDL Receptor | \nRat, HSCs and hepatocytes | \nSpectacular progress of pathophysiological symptoms in liver fibrosis | \n[50] | \n
08 | \nPEG-SLN | \nGT, CHO | \nSolvent-emulsification method | \nPTX | \nHepatocytes | \nHepG2, MCF7, PANC-1 | \nHigher liver bioaccumulation of PTX | \n[51] | \n
09 | \nG-SLN | \nCOMP | \nHigh-pressure homogenization | \nCurB | \nASGP Receptor | \nWistar rats | \nEnhanced antitumor and hepatoprotective activity | \n[52] | \n
List of SLNs and their different ligand conjugated forms for liver cell targeting.
Breast cancer is the most common form of cancer and the second most deadly disease among the woman around the globe. The breast cancer new incidences and mortality rate has been increased by 20 and 14% since 2008.
\nRecently, controlled release of the drugs to the targeted site of the disease using a nanocarrier vehicle is getting more attention as it enhances the therapeutic efficacy of the drugs. Solid lipid nanoparticulate (SLN) formulations possess an endless potential to deliver active chemotherapeutic molecules in a programmed prototype to improve bioavailability and nullify the side-effects. The bio-compatibility and bio-degradability characteristics of SLNs promise to offer a lesser toxic product as compared to polymeric nanoparticles which forced to consider it as an idealistic targeted drug delivery system for breast cancer therapy [5].
\nPhotodynamic therapy is one of the emerging approaches in the treatment of cancer which comprises application of a photosensitizer followed by laser irradiation of tumor lesions. Temoporfin (TP), a photosensitizer loaded in thermoresponsive SLNs were developed with an objective to improve anticancer activity through site specific drug delivery. The copolymer poly(ethylene oxide)-block-poly(ε-caprolactone) copolymers (PEO45-b-PCL7) were synthesized by the mechanism of catalyst-free ring opening polymerization of ε-caprolactone which was initiated by poly(ethylene oxide) monomethyl ether(MPEO). These copolymers were acts as a stabilizer in the preparation of thermoresponsive SLN. The stability study report revealed that the developed SLNs had higher stability in human serum within the blood transport to tumor tissue.
Transition metal complex (e.g., Manganese II complex [Mn2(μ(C6H5)2CHCOO)2(bipy)4]± 2) has been extensively used for cancer therapy nowadays due to its potential anticancer activity (interact with the DNA). Mn(II) complex loaded SLNs were developed that showed superior cytotoxicity activity on breast cancer cells. The zeta potential value of the product was higher indicating good physical stability and dispersion quality of the SLNs. Cell proliferation assay revealed that the normal cell death rate was lower with Mn(II) SLNs which indicated lesser toxicity of the product to the normal cell. Moreover, higher early apoptosis rate was observed with Mn(II) complex SLN as compared to Mn(II) alone [54].
\nFucose receptors are overexpressed in the breast cancer cell. Thus, conjugation of fucose to SLNs was proposed to deliver the drug specifically to breast cancerous cells. Fucose conjugated methotrexate (MTX) loaded SLNs were developed to achieve enhanced targeting potential for breast cancer cells. Fucosylation of MTX-SLNs was related with opening of fucose ring and reaction of its aldehyde group with free amino functionalities expressed over the surface of MTX-SLNs in sodium acetate buffer (pH 4.0). The above process led to the formation of Schiff’s base (–N=CH). The Schiff’s base might be reduced to secondary amine (–NHCH2) and establish equilibrium with Schiff’s base. Physical stability of prepared SLNs was higher which could be due to positive zeta potential value that provides repulsive interaction between nanosized lipid particles preventing particle aggregation. The
The folate receptor (FR) is one of the most widely evaluated receptor for active targeting of anticancer therapeutics in the case of in breast cancer cells. Folic acid has many advantages over antibody ligands such as small size, non-immunogenicity, non-toxicity, ease of handling, stability and low cost [56]. Several researchers had reported earlier that the FA functionalized SLNs were able to deliver the chemotherapeutic agent, particularly to the cancerous cells. Thus, FA functionalized SLNs co-encapsulated with Docetaxel (DTX) and Curcumin (CUR) were successfully developed to enhance its therapeutic efficacy against breast cancer cells. FA-stearic acid (FA–SA) conjugate was synthesized by classical 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) chemistry and incorporated in the DTX-CUR-SLN. Additionally, PEG–stearic acid (PEG–SA) was incorporated to obtain FA-DTX-CUR-SLN. The DTX-CUR-SLN and FA-DTX-CUR-SLN formulations were found to be stable at refrigerated condition for 2 months. Both the formulations showed sign of instability at accelerated condition (25°C/65% RH). The developed FA functionalized SLNs exhibited improved pharmacokinetic parameters, superior cancer cell targeting efficiency, and improved therapeutic efficacy of DTX. Folic acid was believed to be responsible for the targeting efficacy of the developed SLNs to the breast cancer cell. This conjugated system showed significant increase in area under the curve and mean residence time of the drug. Co-conjugation (FA and PEG) to SLNs co-encapsulated with DTX and CUR responsible for synergistic activity of both DTX and CUR. Moreover, bioaccumulation of DTX in heart and kidney was found very low which signified avoidance of vital organ toxicity [57].
\nThe sphingosine-1-phosphate (S1P), phytosphingosine, ceramides, and sphingosine are the metabolites of sphingolipids and are reported as essential structural components of cell membranes or important mediators of cellular process that regulate the proliferation, survival, and death of cells. Moreover, sphingosines including N,N,N-trimethylsphingosine (TMP-I) have been reported for their role as a negative modulator of transmembrane signaling through protein kinase C (PKC) as well as an inhibitor of sphingosine kinase-1 (SK-1), controlling the various membrane-associated signaling mechanisms associated with cell growth and inhibitory apoptosis in tumor cells [58]. Ceramide, a kind of sphingosine conjugated with fatty acid residue, is also reported to enhance the sensitivity of MDR-acquired cancer cell lines to chemotherapeutic agents [59]. Thus, attempts were made to employ ceramide (CD) and trimethylphytosphingosine-iodide (TMP-I) as a targeting agent for docetaxel (DTX) loaded SLNs. The prepared SLNs were physically stable without any significant change in their physical appearance, drug content, and particle size over a period of 8 weeks at 4°C. CD enhanced the DTX sensitivity in MDR-acquired cancer cell lines.
List of SLNs and their different ligand conjugated form for breast cancer cell targeting have been summarized in Table 4.
\nSl. no | \nSLN (Type) | \nLipid(s) | \nDrugs | \nPreparation method | \nTarget | \nModel | \nComments | \nRef. | \n
---|---|---|---|---|---|---|---|---|
01 | \nSLN | \nTD | \nTMP | \nModified hot homogenization and ultrasonication method | \nBreast Cancer cell | \n4T1, MDA-MB-231, Female Nu/Nu mice- MDA-MB-231 | \nExhibited improved phototoxicity and anticancer efficacy | \n[53] | \n
02 | \nMn (II) Complex-SLN | \nCOMP | \nMn (II) complex | \nHot homogenization method | \nBreast Cancer cell | \nMCF-7 and HUVEC cell line | \nPossessed superior anticancer activity with reduced toxic effect. | \n[54] | \n
03 | \nF-SLN | \nPL90NG, PL, STA, GEL | \nMTX | \nHot microemulsion method | \nFucose Receptor | \nMCF-7 Cell line & Female SD rat | \nImproved bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs. | \n[55] | \n
04 | \nFA-PEG-SLN | \nGMS, SA | \nCUR, DTX | \nModified ethanol injection method | \nFolic acid Receptor | \nMCF-7 &MDA-MB-231Cell line. Female Wistar Rat | \nSynergistic cancer efficacy due to coencapsulation of DTX and CRM along with targeted delivery of drugs | \n[57] | \n
05 | \nCD-TMP I-SLN | \nPC, TMS, | \nDTX | \nHigh-pressure homogenization method | \nCD & TMP-1 | \nMCF-7 cell, MCF-7/ADR cells | \nSignificant increased antitumor efficacy with targeted drug delivery | \n[60] | \n
List of SLNs and their different ligand conjugated forms for breast cancer cell targeting.
The eye is one of the delicate organs of human and one of the most delicate routes of drug delivery. However, the eye poses unique challenges relative to drug delivery due to the ocular anatomical and physiological constraints. SLNs are one of the promising targeted DDS for an eye. Numerous drugs such as antibiotics, plasmids, anti-inflammatory, and immunosuppressive agents were encapsulated in SLNs for the treatment of ophthalmic disorders.
\nCorneal neovascularization (CNV), a sight-threatening condition is caused due to various inflammatory settings including chemical injury. Single-stranded proline-modified short hairpin anti-angiopoietin-like protein 2 (ANGPTL2 RNA) interference molecules acts as potent angiogenic and pro-inflammatory factor and is used for the treatment of CNV [61]. Thus, ANGPTL2 RNA loaded SLNs were developed to deliver the interference molecule specifically to the retina. The single-stranded RNAi (pshRNA) loaded SLNs exhibit high stability
X-linked juvenile retinoschisis (XJR), a retinal degenerative disorder caused by mutation in the RS1 gene encoding a retinoschisin [63]. Among non-viral vectors, solid lipid nanoparticles (SLNs) represent one of the most effective lipid-based colloidal carriers, and for gene delivery to the posterior segment of the eye [64]. Plasmid (human RS1 gene) loaded SLNs were developed for the treatment of XJR diseases which showed significant improvement of the retinal structure with photoreceptor specific expression of the RS1 gene [65].
\nTobramycin (TMC) is one of the most preferable drugs to treat vitreoretinal diseases, such as bacterial infections, endophthalmitis, cytomegalovirus retinitis (CMV), uveitis, proliferative vitreoretinopathy (PVR), diabetic retinopathy, age-related macular degeneration [66]. Thus TMC loaded mucoadhesive SLNs were developed which showed higher bioaccumulation of drugs in most of the ocular tissues and was able to penetrate into the retina. Moreover, it resulted in enhanced intraphagocytic antibiotic concentration in polymorphonuclear granulocytes and superior bactericidal activity against
Indomethacin (IMC), a topical non-steroidal anti-inflammatory drug (NSAID) is used for ocular inflammatory disorders such as conjunctivitis, uveitis, cystoid macular edema, and anterior segment inflammation, including post-operative pain following cataract surgery [68]. Chitosan (Cs) coated IMC loaded SLNs (IMC-Cs-SLN) were developed to deliver NSAID to the posterior segment of ocular tissues and for improving the pre-corneal residence time and transcorneal permeability characteristics. For surface modification of the developed SLNs, the chitosan was incorporated into the aqueous phase prior to preparation of the SLNs. The developed SLNs were stable in terms of drug loading, EE, and less drug expulsion during storage at 40°C for 90 days. The SLNs showed higher bioaccumulation of IMC in the ocular tissues. The IMC-Cs-SLN showed superior trans-membrane IMC permeation characteristics which were due to penetration enhancing properties of Cs [69].
\nBetaxolol hydrochloride (BH) is widely used for the treatment of ocular hypertension and open-angle glaucoma in clinical therapeutics. However, it faces certain limitations like low bioavailability and pre-ocular retention, and some side effects. In order to overcome these limitations acid treated montmorillonite (Mt)- Betaxolol Hydrochloride (BH) nanocomposite encapsulated SLNs (Mt-BH-SLNs) were developed. An acid-treated montmorillonite (acid-Mt) was first intercalated with BH in the interlayers and this nanocomposite was encapsulated by SLNs. The developed Mt-BH-SLNs possess good stability. Long term irritation test reported that the (Mt-BH-SLNs) showed no damage for cornea and conjunctiva. The corneal hydration level of Mt-BH-SLNs was higher (78.25 ± 0.63)% indicating higher drug corneal permeability and absence of irritation to the cornea. Thus, Mt-BH-SLNs could be used for effective management of glaucoma [70].
\nKetoconazole (KTZ) is a broad spectrum antifungal agent, with high lipo-solubility [71] but a short ocular half-life (elimination half-life is 19 min in aqueous humor and 43 min in cornea) [72] and very poor solubility (0.04 mg/ml). Ketoconazole (KTZ) loaded PEGylated SLNs were developed for targeted delivery of KTZ to the posterior part of the eye for treatment of fungal infection. It showed higher bioavailability both in the aqueous and vitreous humor with significant antifungal potential. The
List of SLNs and their different ligand conjugated forms for eye targeting have been summarized in Table 5.
\nSl. no | \nSLN (Type) | \nLipid(s) | \nDrugs | \nPreparation method | \nTarget | \nModel | \nComments | \nRef. | \n
---|---|---|---|---|---|---|---|---|
01 | \nSLN | \nDSGPC, CHO | \nANGPTL2 RNA | \nHydration method followed by extrusion | \nRetina | \nC57BL/6 mice | \nInhibition of expression of ANGPTL2mRNA, Reduction in angiogenesis area | \n[62] | \n
02 | \nSLN | \nPRE | \nHuman RS1 gene | \nSolvent emulsification followed by evaporation | \nRetina | \n661W, RS1h-deficient mouse | \nImprovement of the retinal structure | \n[65] | \n
03 | \nSLN | \nSA | \nTMC | \nWarm o/w microemulsion method | \nAqueous humor | \nAlbino rabbit | \nSuperior bactericidal activity | \n[67] | \n
04 | \nCs-SLN | \nGB | \nIMC | \nHot homogenization | \nPosterior segment of ocular tissue | \nWhite albino Rabbits | \nImproved biodistribution of IMC at posterior segment | \n[69] | \n
05 | \nMt-SLNs | \nPC, GMS | \nBH | \nEmulsion evaporation-low temperature solidification method | \nCornea and Conjunctiva | \nRabbit | \nSignificantly reduced inflammation, No irritation | \n[70] | \n
06 | \nPEG-SLNs | \nCOMP | \nKTZ | \nEmulsification followed by high pressure homogenizer | \nUpper posterior eye | \nARPE-19 & RCE Cell line, Rat | \nSuperior antifungal activity | \n[73] | \n
07 | \nMultifunctional SLNs | \nCP | \nBAI (Drug) C IR-780 (Diagnostic agent) | \nModified solvent-diffusion method | \nColorectal part | \nLoVo, CHO-K1 | \nImaging, Superior cytotoxicity | \n[75] | \n
08 | \nSIA-PEGylated SLN | \nGMS, OA | \nDXM | \nSolvent diffusion method | \nE-selectin receptor | \nHUVECs, ICR male Mice | \nTargeted delivery of DXM for ischemia-reperfusion-induced injury-induced AKI | \n[78] | \n
List of SLNs and their different ligand conjugated forms for eye, colon and kidney targeting.
Combination of nanocarriers and electroporation techniques is named as electropermeabilization which is commonly used for enhancing drug transport. The Cyanine–type IR 780 and Baicalein (BAI) co-encapsulated SLNs were developed for both imaging and therapy of colorectal carcinoma where cyanine–type IR 780 and baicalein (flavonoid derivative) were acting as a diagnostic agent (photosensitizer) and therapeutic cargo respectively. For preparation of SLNs the organic phase was prepared by dissolving IR-780, BAI, and melted lipid in dichloromethane. The organic phase was then added dropwise to hot aqueous phase containing surfactant under vigorous stirring. Supplementary material (flavonoids) facilitated in the reduction of dose and reduction in normal cell toxicity in cancer chemotherapy. The external electric field pulses applied in electroporation helped in increased of cell membrane permeability, either by generating transient pores or membrane electropermeabilization [74]. Electropermeabilization mediated administration of the developed SLNs showed cytoskeletal abnormalities more significantly then without electropermeabilization. The prepared SLNs particles were with good physical stability. With electroporation support, the developed SLNs showed increased p53 and manganese superoxide dismutase expression with significant higher cytotoxicity, thus validating their suitability for combined therapy and molecular imaging simultaneously [75].
\nList of SLNs and their different ligand conjugated form for colon targeting have been summarized in Table 5.
\nIcariin (IRN) is widely used as traditional Chinese medicine for the treatment of kidney diseases and reinforce yang. The PEG surface modified Icariin (IRN) loaded SLNs (PEG-IRN-SLNs) was developed for targeted delivery of IRN to the kidney and to improve the bioavailability. The SLN was prepared by high temperature melt-cool solidification method. Upon comparing with IRN solution it was revealed from the pharmacokinetic study that the biological half-life (t1/2) and area under curve (AUC) of PEG-IRN-SLN was 7-fold and 4-fold higher. Biodistribution study revealed that IRN concentration in kidney tissues was significantly increased. Moreover, the relative target efficiency to kidney tissues was 79% and relative tissue exposure was 16.95. Thus the develop SLN could be helpful in the treatment of kidney diseases [76].
\nE-selectin is a promising target for the site-specific delivery of anti-inflammatory agents. Several researchers have reported that sialic acid (SA)-mediated micelles could be specifically internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) via the specific binding between SA and E-selectin receptor [77]. Sialic acid (SIA) conjugated PEGylated dexamethasone (DXM) loaded SLNs (SIA-PEGylated-DXM-SLN) were developed to deliver DXM specifically to the kidney and to improve the therapeutic efficacy of DXM for renal ischemia–reperfusion injury (IRI)-induced acute renal injury. The Sialic acid (SIA) conjugated PEGylated DXM (SIA-PEG-DXM) was synthesized by adding PEG-DXM, dicyclohexylcarbodiimide (DCC), and 4-dimethylaminopyridine (DMAP) into anhydrous dimethyl formamide (DMF) followed by addition of SIA into the solution. The resulting mixture was stirred for obtaining SIA-PEG-DXM. The crude product was purified by dialysis against deionized water for 2 days, followed by lyophilization. The developed SLNs potentially had good colloidal stability in human body. The study revealed that the apoptotic human umbilical vein endothelial cells (HUVECs) were significantly decreased. It indicated the suitability of SIA-PEGylated-SLNs for internalization by the inflamed vascular endothelial cells. Biodistribution study revealed higher renal accumulation of DXM (range 2.7- to 5.88-fold higher) after 6 h of intravenous administration. The Pharmacodynamic study revealed that higher blood biochemical indexes, histopathological changes, oxidative stress levels, and pro-inflammatory cytokines which indicated improved renal function by the influence of SIA-PEGylated DXM [64].
\nList of SLNs and their different ligand conjugated form targeting to the kidney have been summarized in Table 5.
\nThough drug targeting to a specific site in the body is an interesting approach, it is a highly challenging task. Despite that a large variety of smart nanocarriers have been developed for drug targeting in recent years, SLN has achieved a special status among them and can be employed for both passive as well as active targeting. These can be employed for delivering not only the drug but also antibody, proteins, genes, imaging agents etc. and bring about increased cellular uptake at the targeted disease sites. Moreover, surface modification of SLNs through conjugation of various ligands on SLNs surfaces helped in enhancing its targeting efficacy in terms of cellular binding, uptake and intracellular transport to different cells as well as organs and ensure its greatest potentiality to combat wide ranges of diseases. However, the intrinsic complexity of biological environments strongly influences its functionality and often complicates their effective use for therapeutic treatments. Therefore, a deeper knowledge and understanding of the real interactions involved in the diseased tissues is fundamental for the development of therapeutic protocols of SLNs.
\nThe authors confirm that this article content has no conflicts of interest.
AM | alveolar macrophages |
ANGPTL2 RNA | single-stranded proline-modified short hairpin anti-angiopoietin-like protein 2 |
AP-E | apolipoprotein E |
ASGP | asialoglycoprotein |
BAI | baicalein |
BBR | berberine |
BCL | baicalin |
BH | betaxolol hydrochloride |
CHO | cholesterol |
CIR-780 | cyanine-type IR-780 |
CMP | camptothecin |
CO | cholesterol oleate |
COMP | compritol 888 ATO |
CP | cetyl palmitate |
CRM | carmustine |
c-SLN | cationic SLN |
CSPT | cisplatin |
Cs-SLN | chitosan coated SLNs |
CUR | curcumin |
CurB | curcumin B |
DM | dimyristoyl |
DMPC | 1,2-dimyristoyl-sn-glycero-3-phospho-choline |
DSPE | Distearoylphosphatidyl-ethanolamine |
DSPEG | 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] |
DSGPC | 1,2-distearoyl-sn-glycero-3-phosphocholine |
DTX | docetaxel |
DXM | dexamethasone |
FA-PEG-SLN | folic acid-polyethylene glycol cross conjugated SLN |
FB | Ficus benjamina |
FR | folate receptor |
F-SLN | fucose conjugated SLN |
Ft-SLN | folate conjugated SLN |
GB | glyceryl behenate |
GEL | Gelucire®50/13 |
GL | glycerol |
GMS | glyceryl monostearate |
GS | glyceryl stearate |
G-SLNs | galactosylated lipid conjugated SLNs |
GT | glycerol trioleate |
GTP | glyceryl tripalmitate |
GTS | Glycerol tristearate |
HSC | hepatic stellate cells |
IMC | indomethacin |
LDL | low density lipid |
LfR | lactoferrin receptor |
Lf-SLN | lactoferrin SLN |
KTZ | ketoconazole |
MIC | minimum inhibitory concentration |
Mn (II) complex | [Mn2(l (C6H5)2CHCOO)2(bipy)4](bipy)(ClO4)2 complex |
MR | mannose receptor |
Msy-SLN | mannosylated SLN |
Mt. | intercalated montmorillonite SLN |
MTX | methotrexate |
PA | palmitic acid |
PC | phosphatidylcholine |
PEG-SLN | PEGylated SLNs |
PL | phospholipid |
PL90NG | Phospholipon 90NG |
PP | primaquine phosphate |
PRE | Precirol ATO5 |
POPC | 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine |
PTX | paclitaxel |
RIF | rifampicin |
RFB | rifabutin |
RSV | resveratrol |
RLZ | riluzole |
SA | stearic acid |
SFB | sorafenib |
SL | soya lecithin |
SIA | sialic acid |
siRNA | small interfering RNA |
SD | Sprague-Dawley |
SP | soybean phospholipid |
SPC | soya phosphatidylcholine |
STA | stearyl amine |
TD | 1-tetradecanol |
TMC | tobramycin |
TMP | temoporfin |
TMP-I | trimethylphytosphingosine-iodide |
TMS | trimyristin |
TP | tripalmitate |
TSN | tristearin |
VIN | vinpocetine |
WGA-SLN | wheat germ agglutinin conjugated SLN |
3D7 | asexual intraerythrocytic stage of P. falciparum laboratory strain (3D7) |
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Interaction Assays",subtitle:null,isOpenForSubmission:!1,hash:"1bed553d74f0565c89758a7159647634",slug:"protein-protein-interaction-assays",bookSignature:"Mahmood-ur-Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/6635.jpg",editedByType:"Edited by",editors:[{id:"185476",title:"Dr.",name:"Mahmood-ur-Rahman",middleName:null,surname:"Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-ur-Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"780",title:"Proteomics",subtitle:"Human Diseases and Protein Functions",isOpenForSubmission:!1,hash:"a90c4e5b369d27036134a3c66ce1cb26",slug:"proteomics-human-diseases-and-protein-functions",bookSignature:"Tsz-Kwong Man and Ricardo J. Flores",coverURL:"https://cdn.intechopen.com/books/images_new/780.jpg",editedByType:"Edited by",editors:[{id:"35047",title:"Prof.",name:"Tsz Kwong",middleName:null,surname:"Man",slug:"tsz-kwong-man",fullName:"Tsz Kwong Man"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:9,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"28196",doi:"10.5772/31776",title:"Exploring the Role of Biomarkers for the Diagnosis and Management of Traumatic Brain Injury Patients",slug:"exploring-the-role-of-biomarkers-for-the-diagnosis-and-management-of-traumatic-brain-injury-patients",totalDownloads:3015,totalCrossrefCites:9,totalDimensionsCites:22,abstract:null,book:{id:"780",slug:"proteomics-human-diseases-and-protein-functions",title:"Proteomics",fullTitle:"Proteomics - Human Diseases and Protein Functions"},signatures:"Linda Papa",authors:[{id:"88648",title:"Dr.",name:"Linda",middleName:null,surname:"Papa",slug:"linda-papa",fullName:"Linda Papa"}]},{id:"66145",doi:"10.5772/intechopen.83426",title:"New Insights into the Mechanisms Underlying NEDD8 Structural and Functional Specificities",slug:"new-insights-into-the-mechanisms-underlying-nedd8-structural-and-functional-specificities",totalDownloads:992,totalCrossrefCites:6,totalDimensionsCites:9,abstract:"Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins are small polypeptides that are conjugated to substrates affecting their activity and stability. Cells encode “receptors” containing Ub-/Ubl-binding domains that interpret and translate each modification into appropriate cellular responses. Among the different Ubls, NEDD8, which is the ubiquitin’s closest relative, retains many of the structural determinants that enable ubiquitin the ability to target proteins to degradation. Nevertheless, the direct involvement of NEDD8 conjugation to proteasome recruitment has been proved only in a few cases. To date, well-defined major NEDD8 substrates are primarily members of the cullin family, and cullin neddylation does not appear to mark these proteins for degradation. Various studies have demonstrated that selectivity between ubiquitin and NEDD8 is guaranteed by small but substantial differences. Nevertheless, several issues still need to be addressed, mainly concerning which interaction surfaces mediate NEDD8 function and what domains recognize them. Recently, two novel domains identified in KHNYN and N4BP1 proteins have shed new light on this research area. Here, I discuss some recent reports that contributed to shed light on the mechanisms underlining the discrimination between ubiquitin and NEDD8. Understanding the details of these molecular mechanisms represents a prominent facet for the identification of new therapeutic targets.",book:{id:"8301",slug:"ubiquitin-proteasome-system-current-insights-into-mechanism-cellular-regulation-and-disease",title:"Ubiquitin Proteasome System",fullTitle:"Ubiquitin Proteasome System - Current Insights into Mechanism Cellular Regulation and Disease"},signatures:"Elena Santonico",authors:[{id:"271923",title:"Dr.",name:"Elena",middleName:null,surname:"Santonico",slug:"elena-santonico",fullName:"Elena Santonico"}]},{id:"28199",doi:"10.5772/31082",title:"F0F1 ATP Synthase: A Fascinating Challenge for Proteomics",slug:"f0f1-atp-synthase-a-fascinating-challenge-for-proteomics",totalDownloads:5557,totalCrossrefCites:2,totalDimensionsCites:8,abstract:null,book:{id:"780",slug:"proteomics-human-diseases-and-protein-functions",title:"Proteomics",fullTitle:"Proteomics - Human Diseases and Protein Functions"},signatures:"Federica Dabbeni-Sala, Amit Kumar Rai and Giovanna Lippe",authors:[{id:"85523",title:"Prof.",name:"Giovanna",middleName:null,surname:"Lippe",slug:"giovanna-lippe",fullName:"Giovanna Lippe"},{id:"149272",title:"Dr.",name:"Federica",middleName:null,surname:"Dabbeni-Sala",slug:"federica-dabbeni-sala",fullName:"Federica Dabbeni-Sala"},{id:"149273",title:"Dr.",name:"Amit",middleName:null,surname:"Kumar Rai",slug:"amit-kumar-rai",fullName:"Amit Kumar Rai"}]},{id:"65025",doi:"10.5772/intechopen.82883",title:"E3 Ubiquitin Ligases in Cancer and Their Pharmacological Targeting",slug:"e3-ubiquitin-ligases-in-cancer-and-their-pharmacological-targeting",totalDownloads:1681,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Ubiquitination plays many critical roles in protein function and regulation. Consequently, mutation and aberrant expression of E3 ubiquitin ligases can drive cancer progression. Identifying key ligase-substrate relationships is crucial to understanding the molecular basis and pathways behind cancer and toward identifying novel targets for cancer therapeutics. Here, we review the importance of E3 ligases in the regulating the hallmarks of cancer, discuss some of the key and novel E3 ubiquitin ligases that drive tumor formation and angiogenesis, and review the clinical development of inhibitors that antagonize their function. We conclude with perspectives on the field and future directions toward understanding ubiquitination and cancer progression.",book:{id:"8301",slug:"ubiquitin-proteasome-system-current-insights-into-mechanism-cellular-regulation-and-disease",title:"Ubiquitin Proteasome System",fullTitle:"Ubiquitin Proteasome System - Current Insights into Mechanism Cellular Regulation and Disease"},signatures:"Joseph Y. Ong and Jorge Z. Torres",authors:[{id:"186645",title:"Dr.",name:"Jorge",middleName:null,surname:"Torres",slug:"jorge-torres",fullName:"Jorge Torres"},{id:"264944",title:"Mr.",name:"Joseph",middleName:null,surname:"Ong",slug:"joseph-ong",fullName:"Joseph Ong"}]},{id:"28201",doi:"10.5772/31113",title:"Identification of the Novel Plasminogen Receptor, Plg-RKT",slug:"identification-of-the-novel-plasminogen-receptor-plg-rkt",totalDownloads:2435,totalCrossrefCites:2,totalDimensionsCites:5,abstract:null,book:{id:"780",slug:"proteomics-human-diseases-and-protein-functions",title:"Proteomics",fullTitle:"Proteomics - Human Diseases and Protein Functions"},signatures:"Lindsey A. Miles, Nicholas M. Andronicos, Emily I. Chen, Nagyung Baik, Hongdong Bai, Caitlin M. Parmer, Shahrzad Lighvani, Samir Nangia, William B. Kiosses, Mark P. Kamps, John R. Yates III and Robert J. Parmer",authors:[{id:"85634",title:"Dr.",name:"Lindsey A.",middleName:null,surname:"Miles",slug:"lindsey-a.-miles",fullName:"Lindsey A. Miles"},{id:"85772",title:"Dr.",name:"Nicholas M.",middleName:null,surname:"Andronicos",slug:"nicholas-m.-andronicos",fullName:"Nicholas M. Andronicos"},{id:"85773",title:"Dr.",name:"Emily I.",middleName:null,surname:"Chen",slug:"emily-i.-chen",fullName:"Emily I. Chen"},{id:"85775",title:"MSc.",name:"Nagyung",middleName:null,surname:"Baik",slug:"nagyung-baik",fullName:"Nagyung Baik"},{id:"85776",title:"Dr.",name:"Hongdong",middleName:null,surname:"Bai",slug:"hongdong-bai",fullName:"Hongdong Bai"},{id:"85777",title:"Ms.",name:"Caitlin M.",middleName:null,surname:"Parmer",slug:"caitlin-m.-parmer",fullName:"Caitlin M. Parmer"},{id:"85778",title:"Dr.",name:"William B.",middleName:null,surname:"Kiosses",slug:"william-b.-kiosses",fullName:"William B. Kiosses"},{id:"85780",title:"Dr.",name:"John R.",middleName:null,surname:"Yates, III",slug:"john-r.-yates-iii",fullName:"John R. Yates, III"},{id:"85781",title:"Dr.",name:"Robert J.",middleName:null,surname:"Parmer",slug:"robert-j.-parmer",fullName:"Robert J. Parmer"},{id:"123594",title:"Dr.",name:"Samir",middleName:null,surname:"Nangia",slug:"samir-nangia",fullName:"Samir Nangia"},{id:"123595",title:"Dr.",name:"Shahrzad",middleName:null,surname:"Lighvani",slug:"shahrzad-lighvani",fullName:"Shahrzad Lighvani"}]}],mostDownloadedChaptersLast30Days:[{id:"70577",title:"Proteoforms: General Concepts and Methodological Process for Identification",slug:"proteoforms-general-concepts-and-methodological-process-for-identification",totalDownloads:924,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The term proteoform is used to denote all the molecular forms in which the protein product of a single gene can be found. The most frequent processes that lead to transcript modification and the biological implications of these changes observed in the final protein product will be discussed. Proteoforms arising from genetic variations, alternatively spliced RNA transcripts and post-translational modifications will be commented. This chapter will present an evolution of the techniques used to identify the proteoforms and the importance of this identification for understanding of biological processes. This chapter highlights the fundamental concepts in the field of top-down mass spectrometry (TDMS), and provides numerous examples for the use of knowledge obtained from the identification of proteoforms. The identification of mutant proteins is one of the emerging areas of proteogenomics and has the potential to recognize novel disease biomarkers and may point to useful targets for identification of therapeutic approaches.",book:{id:"9352",slug:"proteoforms-concept-and-applications-in-medical-sciences",title:"Proteoforms",fullTitle:"Proteoforms - Concept and Applications in Medical Sciences"},signatures:"Jucélia da Silva Araújo and Olga Lima Tavares Machado",authors:[{id:"30130",title:"Dr.",name:"Olga Lima Tavares",middleName:null,surname:"Machado",slug:"olga-lima-tavares-machado",fullName:"Olga Lima Tavares Machado"},{id:"310148",title:"Dr.",name:"Jucelia",middleName:null,surname:"Da Silva Araujo",slug:"jucelia-da-silva-araujo",fullName:"Jucelia Da Silva Araujo"}]},{id:"65025",title:"E3 Ubiquitin Ligases in Cancer and Their Pharmacological Targeting",slug:"e3-ubiquitin-ligases-in-cancer-and-their-pharmacological-targeting",totalDownloads:1681,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Ubiquitination plays many critical roles in protein function and regulation. Consequently, mutation and aberrant expression of E3 ubiquitin ligases can drive cancer progression. Identifying key ligase-substrate relationships is crucial to understanding the molecular basis and pathways behind cancer and toward identifying novel targets for cancer therapeutics. Here, we review the importance of E3 ligases in the regulating the hallmarks of cancer, discuss some of the key and novel E3 ubiquitin ligases that drive tumor formation and angiogenesis, and review the clinical development of inhibitors that antagonize their function. We conclude with perspectives on the field and future directions toward understanding ubiquitination and cancer progression.",book:{id:"8301",slug:"ubiquitin-proteasome-system-current-insights-into-mechanism-cellular-regulation-and-disease",title:"Ubiquitin Proteasome System",fullTitle:"Ubiquitin Proteasome System - Current Insights into Mechanism Cellular Regulation and Disease"},signatures:"Joseph Y. Ong and Jorge Z. Torres",authors:[{id:"186645",title:"Dr.",name:"Jorge",middleName:null,surname:"Torres",slug:"jorge-torres",fullName:"Jorge Torres"},{id:"264944",title:"Mr.",name:"Joseph",middleName:null,surname:"Ong",slug:"joseph-ong",fullName:"Joseph Ong"}]},{id:"65109",title:"Ubiquitin Signaling in Regulation of the Start of the Cell Cycle",slug:"ubiquitin-signaling-in-regulation-of-the-start-of-the-cell-cycle",totalDownloads:1578,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation.",book:{id:"8301",slug:"ubiquitin-proteasome-system-current-insights-into-mechanism-cellular-regulation-and-disease",title:"Ubiquitin Proteasome System",fullTitle:"Ubiquitin Proteasome System - Current Insights into Mechanism Cellular Regulation and Disease"},signatures:"Michael James Emanuele and Taylor Paige Enrico",authors:[{id:"264977",title:"Dr.",name:"Michael",middleName:null,surname:"Emanuele",slug:"michael-emanuele",fullName:"Michael Emanuele"},{id:"282200",title:"Ms.",name:"Taylor",middleName:null,surname:"Enrico",slug:"taylor-enrico",fullName:"Taylor Enrico"}]},{id:"60432",title:"Protein-Based Detection Methods for Genetically Modified Crops",slug:"protein-based-detection-methods-for-genetically-modified-crops",totalDownloads:1430,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"The generation of genetically modified (GM) crops is rapidly expanding each and every year around the world. The well-being and quality assessment of these harvests are vital issues with respect to buyers’ interests. This drove the administrative specialists to execute an arrangement of extremely strict strategies for the endorsement to develop and use GMOs and to produce an interest in scientific techniques equipped for identifying GM crops. The GM crops have been added to the effective fuse of various attributes by presenting transgenes, for example, Bacillus thuringiensis (Bt) insecticidal qualities, in various crop species. GM crops give critical financial, natural, well-being and social advantages to both small and large agriculturists. The detection strategies incorporate either DNA-based or protein-based measures. Different immunoassays or catalyst connected immunosorbent tests are delicate and more affordable; however, they need experienced technicians. A very simple method, that is, immunochromatographic (ICS) test, is set up in the world, which is modest, compact and simple to utilize. The ICS is a semiquantitative method for indicative screening and semi-measurement of new remote proteins presented through hereditary change of plants. The strip is the easiest method for the assessment of several Bt crop plants for insecticidal quality.",book:{id:"6635",slug:"protein-protein-interaction-assays",title:"Protein-Protein Interaction Assays",fullTitle:"Protein-Protein Interaction Assays"},signatures:"Kausar Malik, Haleema Sadia and Muhammad Hamza Basit",authors:[{id:"238750",title:"Prof.",name:"Kausar",middleName:null,surname:"Malik",slug:"kausar-malik",fullName:"Kausar Malik"},{id:"243713",title:"Dr.",name:"Haleema",middleName:null,surname:"Sadia",slug:"haleema-sadia",fullName:"Haleema Sadia"},{id:"243714",title:"Mr.",name:"Muhammad Hamza",middleName:null,surname:"Basit",slug:"muhammad-hamza-basit",fullName:"Muhammad Hamza Basit"}]},{id:"60064",title:"Rapid Endosomal Recycling",slug:"rapid-endosomal-recycling",totalDownloads:1342,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Peripheral membrane proteins are endocytosed by constitutive processes of membrane invaginations, followed by internalization driven by diverse endocytic machinery available at the cell surface. It is believed that after endocytic uptake, cargo proteins proceed either through the endosomal recycling circuit of the cell or travel toward late endosomes for degradation. In this chapter, we analyzed trafficking of seven cargo molecules (transferrin receptor, fully conformed MHC-I, non-conformed MHC-I, cholera-toxin B subunit, CD44, ICAM1, and G-protein-coupled receptor Rae-1) known to use the distinct endocytic route. For that purpose, we developed the software for multicompartment analysis of intracellular trafficking. We demonstrate that all endocytosed molecules are rapidly recycled and propose that the rapid recycling is a constitutive process that should be considered in the analysis of intracellular trafficking of peripheral membrane proteins.",book:{id:"6649",slug:"peripheral-membrane-proteins",title:"Peripheral Membrane Proteins",fullTitle:"Peripheral Membrane Proteins"},signatures:"Hana Mahmutefendić, Gordana Blagojević Zagorac, Senka Maćešić\nand Pero Lučin",authors:[{id:"152008",title:"Prof.",name:"Pero",middleName:null,surname:"Lučin",slug:"pero-lucin",fullName:"Pero Lučin"},{id:"245873",title:"Prof.",name:"Hana",middleName:null,surname:"Mahmutefendić",slug:"hana-mahmutefendic",fullName:"Hana Mahmutefendić"},{id:"245875",title:"Prof.",name:"Gordana",middleName:null,surname:"Blagojević Zagorac",slug:"gordana-blagojevic-zagorac",fullName:"Gordana Blagojević Zagorac"},{id:"245876",title:"Prof.",name:"Senka",middleName:null,surname:"Maćešić",slug:"senka-macesic",fullName:"Senka Maćešić"}]}],onlineFirstChaptersFilter:{topicId:"913",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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