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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
This handbook explains the application of nanoparticles in medical diagnosis and treatment. It is a ready reference on the subject, starting with the introduction to nanoparticles and progressing to synthetic procedures for nanotherapeutics, human disease diagnosis and nanocarrier-based drug delivery. The book also covers information about specific nanoparticle conjugates, in which nanoparticles are combined with drugs or nucleic acid strands (DNA, siRNAs, shRNAs, miRNAs) as well as topics relevant to this field such as immunotherapy and vaccination development strategies. Each chapter also provides references for further reading.A Comprehensive Guide to Nanoparticles in Medicine is an ideal resource for scholars in the fields of medicine, pharmacology and biotechnology who require an understanding about some basic facets of nanoparticles.
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Veröffentlichungsjahr: 2021
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FOREWORD
Drug administration without any side effects is The need of the hour in today’s research. Nanotechnology has emerged as a tool for the creation of nanoparticles that are less than 100nm in size. These nanomaterials have a wide variety of applications in medicine for diagnostic and imaging purposes, and also in targeted drug delivery and gene delivery. Targeted drug delivery may reduce the side effects of the drugs and is the priority research area in nanotechnology. On the other hand, gene deliveries in the form of DNA/siRNA/shRNA/miRNAs are the burning issue in nanomaterial and technology. The invention of immunotherapy and vaccines is the priority of today’s research.
However, even though excellent nanocarriers have been invented, still there are many areas that need to be resolved before their clinical application. How to improve these nanomaterials for practical application in the treatment of diseases is the main question in research today? How can the gene delivery system be improved to make it free from off-target side effects? These were the few questions that are kept in mind while writing this book.
This book written by Dr. Rituparna Acharya is of interest not only for pharmacy students but also for the researchers and students of nanotechnology, biology and the researchers of drug delivery and medical imaging. The book “A Comprehensive Guide to Nanoparticles in Medicine” links academic knowledge with the research in nanomaterials.
PREFACE
This book is intended to focus on the delivery of nanoparticles in several disease conditions. The synthesis methods of these nanoparticles are unique in their approach. The novel diagnostic procedures through nanoparticles are used to identify diseases in humans. The delivery of drugs conjugated with nanoparticles can optimize the dosage level and help in delivering the same to the intended target organ. Various types of nanoparticles, including the organic, inorganic and polymeric in structure are under investigation to deliver them for diagnostic and therapeutic purposes. This book covers various nanoparticle conjugates, for example, when the nanoparticle is conjugated with drugs or DNAs or siRNAs, or shRNAs or miRNAs. All aspects of immunotherapy and vaccination strategy are also included in this book. Up to date information about the nanoparticles used in medicine is the intention of the book.
In particular, chapter 1 discusses the introduction of nanoparticles that are extensively used in medicine. It gives an overview of the proceeding chapters in a consistent manner.
Chapter 2 focuses on the synthesis method of the nanoparticles that are used in medicine. It discusses the advantages and drawbacks of the synthesis methods in detail along with the characteristics and production methods in a step-by-step manner.
Chapter 3 discusses the diagnostic procedures using nanoparticles along with their advantages, disadvantages and their applications in different fields of medicines.
Chapter 4 gives an overview of the characteristics of the nanoparticles that help them to deliver the drug to the target site, their application in medicine and this chapter also discusses the wide variety of nanoparticles that are used for this purpose.
DNA-nanoparticle conjugate is the subject of chapter 5 that presents an overview of the different types of nanoconjugates used in the treatment and diagnosis of disease conditions.
Chapter 6 describes the challenges in the delivery of siRNAs and methods of overcoming those challenges using nanoconjugates. We described the advantages and disadvantages of using siRNA-nanoparticle conjugates in medicine.
shRNA-nanoparticle conjugates are the topic of discussion of chapter 7 that describes the wide variety of nanoparticles that conjugate with shRNAs and targets specific genes for the treatment of a verity of diseases.
Chapter 8 demonstrates the therapeutic approaches using miRNAs. It discusses the challenges of using miRNA in therapeutics and the variety of nanoconjugates used in therapy.
Immunotherapy is the focus area of chapter 9. It discusses the role of nanoparticles in immunotherapy. The wide variety of nanoparticles is used for this purpose and is discussed in this chapter.
Characteristics of nanovaccines are described in chapter 10 and different types of nanoparticles used for vaccination to increase their efficacy are also described in this chapter. Nanoparticles used for immunostimulation are the focus area.
Chapter 11 is the chapter of conclusion that reviews the chapters already discussed in this book. It covers the synthesis method of nanoparticles, along with drug delivery, gene therapy, immunotherapy and vaccination strategies in short.
This book provides a comprehensive coverage of nanoparticles that are used in nanomedicines. It gives an overview of the synthesis methods, diagnostic strategies, drug delivery, gene delivery, immunotherapy and vaccination methods using nanoparticles. The goal of the author is to deliver the readers an up-to-date understanding of nanoparticles in clinical research.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The author declares no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
The success and final outcome of this book required a lot of guidance and assistance from my parents and I am extremely privileged to have got this all along the completion of my book.
I would like to thank my parents who helped me a lot in completing this book.
Introduction of Nanoparticles in Medicine
Rituparna AcharyaAbstract
Nanotechnology is a branch of science that deals with nanomaterials with a size of less than 100nm. These nanoparticles have a wide variety of applications in the field of bioimaging, biosensors, drug delivery, gene therapy, etc. The main advantage of using nanoparticles is that they may be fabricated as desired depending upon the area of application. The size, surface chemistry and physiochemical properties may be changed as required by following the parameters of synthesis. Nanoparticles may also help in RNAi therapy that delivers siRNA, shRNA and miRNAs to the target site. The major drawback of using these RNA molecules in their bare form is the fragile nature that makes them degradable by the enzymes in the blood vascular system. In this regard, nanoparticles protect them from degradation as they may encapsulate the RNA molecules within their structure. There are mainly three types of nanoparticles such as inorganic, organic and polymeric nanoparticles. In this book, we are intended to discuss the wide variety of nanoparticles that are used in biosensing, bioimaging, drug delivery, gene therapy, immunotherapy and vaccination.
INTRODUCTION
After tremendous research effort, a new branch of science originated, known as “Nanotechnology”. The word “Nanotechnology” is the agglomeration of two different words i.e., “Nano” and “Technology”. Nanotechnology deals with particles that have a size of less than 100nm. In the modern era, nanoparticles have a wide range of applications in the field of medicines, information technology, energy, environment, aerospace science, etc. [1-3]. As nanoparticles show improved characteristics in their small dimension, these nanomaterials have a vital role to play in the science of nanotechnology. Due to their outstanding physical, chemical, optical, electronic and biological properties, they open up new avenues of application in the scientific and technological field.
The size, shape, and physiochemical properties of the nanoparticles may be fabricated depending upon their utilization. Diverse size and surface properties make them potential for a wide variety of applications. Their properties may be tailor-made for appropriate applications. Inorganic, organic and polymeric nanoparticles [4, 5] may be used for a variety of applications such as drug delivery [6], bioimaging [7], biosensors [8], molecular tagging, food technology [9], antimicrobial coatings [10], textile manufacturing [11], quantum lasers [12], quantum computers [13], energy and environmental uses, etc. To obtain optimum size and physiochemical properties, the synthesis method of the nanoparticles is essential to study in detail. An appropriate synthesis method should be applied in order to get the desired size and surface property of the nanoparticle. In the present book, we will discuss the synthesis methods, for example, physical, chemical and bio-assisted methods.
Nanoparticles may be used also in the diagnosis of disease conditions [14]. Detection of biological and chemical components may be performed using nanoparticles. By the identification of genetic material and proteins in the body in the early stage of the disease makes the detection method more efficient. So, the diagnostic technique that is sensitive, selective and stable is in demand in the current scenario.
Biosensing method comprises two steps, firstly recognition and binding to the target element, secondly, the transduction of the signal of the binding event. These two components should be efficient enough for proper detection of the target molecule. Thus, the challenge is on the development of both of these recognition and transduction processes. However, the nanoparticles are developing new recognition and transduction methods for accurate detection of the target molecules [15]. Nanoparticles have several physical and chemical characteristics that make them ideal for manufacturing sensitive detection methods [16]. The unique optical, magnetic and electronic properties of the nanoparticles make them ideal for these applications. Moreover, nanoparticles may be conjugated with ligands and bio-macromolecules that help them in the detection system [17-20]. In this book, we will discuss the detection methods invented using nanoparticles for wide variety of disease conditions.
Nanoparticles may also be used as drug delivery vehicles to the target organ [21, 22]. This approach reduces the dosage and side effects of the drugs when used in bare form. Nanoparticles resolve the problems arising from uncontrollable release of drugs, nonspecific distribution, rapid clearance, and low bioavailability [23-25]. Even though a wide variety of nanocarriers is developed by scientists, still, they are associated with unwanted toxicity diminishing their use in nanomedicine. This highlights the design and engineering of the nanocarriers for their use in biotechnology [26-28]. In this book, we are intended to discuss the newly developed nanocarriers with application in drug delivery. We will analyze the main parameters that influence drug delivery in an optimum manner. Further, we will also analyze the challenges and limitations of the newly developed areas in drug delivery.
In recent decades, nanoparticles have received enormous attention for their extraordinary functional property in the application of diagnostic and therapeutic areas. Nanoparticles are chosen as a delivery vehicle of DNA that may help in theranostic applications. Viral vectors for the delivery of plasmid DNA have demonstrated immense immune response. Nanoparticles play a vital role in this respect.
Nanoparticle in conjugation with DNA macromolecules has several applications in the field of molecular diagnosis, biosensing and gene therapy. These approaches have the opportunity to develop low-cost and highly sensitive diagnostic procedures using DNA. The study shows that DNA-nanoparticle conjugates have promising applications in near future. This book is intended to study about the wide variety of nanoparticles and their application in diagnosis and therapy. We have specifically focused on gold, silver and carbon nanoparticles in conjugation with DNA for their application in medical biotechnology.
RNAi therapy has revealed a new avenue of the therapeutic opportunity of several diseases like cancer, genetic diseases, autoimmune diseases and viral infections. siRNAs, shRNAs and miRNAs are the three types of RNAi therapeutic options that may cure many diseases. Among them, siRNAs have entered clinical trials that are being pursued as a curative measure for several diseases. Although they are showing success, still they need to be studied in more detail for their prospective commercial success as therapeutics [29].
Another RNAi therapy is through shRNAs. shRNA-nanoparticles when conjugated together they help in treating several genetic and infectious disease conditions [30-36]. In this book, we will discuss the wide variety of nanoparticles that may be conjugated with shRNAs and used for the treatment of many disease conditions.
The use of miRNAs is also a type of RNAi therapy. Suppression and replacement gene therapies are the main two types of mechanisms that are used for therapeutic applications. To overcome the hurdles of using bare miRNAs, nanoparticles are used. In this book, we will discuss the nanoparticles that help in the delivery of miRNAs encapsulated or in conjugation.
Along with the use of RNAi therapy, nanoparticles are also used for immune modulation. Nanoparticles are approaching a new way of treating diseases. New functionalized capability of the nanoparticles is making them available for immunotherapy. These new materials may have the potential of application in this field. In this book, we are intended to discuss the number of immunostimulators and their conjugation with a wide variety of nanoparticles.
In vaccine delivery, live attenuated microbes, killed microbes or components of microbes are used in traditional therapy. However, live vaccines are not safe for immunocompromised individuals. Moreover, there is a wide range of infectious disease conditions where vaccines are not available. So, recent attention is given to the nanoparticles that may help in antigen delivery. Antigens may be encapsulated within the nanoparticles or may be decorated over the surface to stimulate the immune response. In this book, we will review the characteristics of nanovaccines, along with the types of nanoparticles used for vaccination and also discuss the wide variety of immunostimulators that use nanocarriers.
Overall, this book is intended to deliver facts about the nanoparticles that are used in medicine for diagnostic and therapeutic intervention.
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Rituparna AcharyaAbstract
The ongoing research in nanotechnology has developed a number of different synthesis techniques of nanoparticles from a diverse range of materials such as metals, biological, metal oxides, ceramics, polymers, etc. Nanoparticles have a range of morphological, physical, chemical properties depending upon their synthesis and precursors that are important for their wide variety of applications such as biosensors, drug delivery, gene delivery, diagnostics and theragnostics. This study is intended to give a broader view of various synthesis methods available nowadays in the field of medicinal applications of nanoparticles. It also contains the advantages and shortfalls of the synthesis methods.
INTRODUCTION
Nanotechnology is comprised of two words “nano” and “technology” that means the particles that are less than 100nm in size are synthesized in this method. The wide range of applications of this nanotechnology has led this method to emerge as a cutting edge method of the modern era. The nanomaterials developed by this procedure have unique optical, physical, chemical and biological properties that explore new avenues in the field of science and technology. To get desirable properties nanoparticles can be tailor-made, depending upon their size and shape.
Due to their small size, nanoparticles have divers’ application in various fields. Depending upon the property, they can be used in medicine in the area of drug delivery, biosensor, bioimaging, molecular tagging, gene therapy, etc.
In order to use these nanoparticles in medicine, the most essential aspect is to understand the synthesis method to fabricate a desirable nanocomposite. The proper synthesis method ultimately leads to the formation of the desired size, shape, surface property of the nanoparticle. In this study, we are intended to understand and review the various synthesis methods of nanoparticles.
There are mainly two different approaches for the synthesis of nanoparticles- Top-Down Approach and Bottom-Up Approach. The top-down approach is nothing but the method by which the precursors are bulk counterparts that step by step lead to the generation of fine nanoparticles. Electron beam lithography, milling techniques, photolithography, anodization, ion and plasma etching are some of the commonly used top-down methods for the industrial production of nanoparticles. On the other hand, the bottom-up approach is nothing but the nucleation and coalescence of the molecules that lead to the formation of nanoparticles. This method is applicable for self-assembly of monomer/polymer molecules, laser pyrolysis, Co-precipitation, sol–gel processing, chemical vapor deposition, plasma or flame spraying synthesis and bio-assisted synthesis.
Generally, nanoparticle synthesis method is divided into 3 techniques i.e., Chemical Method, Physical Method and Biological Method (Fig. 1).
CHEMICAL METHODS OF NANOPARTICLE SYNTHESIS
Co-precipitations, sol-gel method, microemulsion, hydrothermal technique, polyol synthesis, microwave-assisted synthesis, chemical vapor deposition, plasma-enhanced chemical vapor deposition are the most commonly used chemical methods for nanoparticle synthesis.
Co-Precipitation
One of the chemical methods of synthesis of nanoparticles is the Co-precipitation method. In this method of synthesis, there is simultaneous occurrence of nucleation, growth, coarsening, and/or agglomeration of the nanoparticle. It is usually chosen when high purity and good stoichiometric control are needed [1]. It is a common reaction for the synthesis of nanoparticles like Fe3O4 [2].
Co-precipitation reaction demonstrates the following characteristics [3, 4]:
The outcome product of this reaction is nothing but the insoluble part of the supersaturated solution.A wide number of small particles emerge from this reaction with large particle size distribution ranging from submicron to tens of microns if proper precautions are not taken in the nucleation stage of synthesis.In the Ostwald ripening procedure, the nucleation stage largely affects the size, morphology, shape and properties of the outcome product.Supersaturation is the ultimate condition that actually leads to the precipitation of the product.Fig. (1)) Schematic diagram of the different types of nanoparticle synthesis methods.The following stages are the methods of production of nanoparticles by the Co-precipitation method [3, 4]:
Nanoparticles are formed from an aqueous solution or by electrochemical reduction and by decomposition of the precursor.Oxides are formed from the reaction.Metal chalconides are formed from this solution.Sonication or microwave is usually used to coprecipitate the product.Co-precipitation method is a facile and convenient approach of the production of nanoparticles due to its following advantages. It also contains some disadvantages as well that are included in the following Table 1 [3-5]:
Sol-Gel Method
The sol-gel method is another procedure of synthesis of nanoparticles in material chemistry. Metal oxides and mixed oxide composites are prepared by this method [6, 7]. Few steps that are hydrolysis, condensation, and drying process, lead to the development of the metal oxides by this method [8-10]. This procedure has better control over the surface property and texture of the material.
Followings are the characteristics of this method [3]:
The commonly used precursors are metal alkoxides or chlorides.Dopes can be used like rare earth metals and organic dyes for the synthesis of the final product [11].The final product can be used as a casting material in the processing and manufacture of ceramics.Metal oxide films can also be produced by this method.The general method of synthesis of the nanoparticle is as follows [4]:
In the liquid phase, all the raw materials are mixed uniformly.Sol is prepared by hydrolysis and polycondensation reactions.Aging of the sols gives rise to the aggregation of colloid particles and formation of gel in three-dimensional network structures.By drying and sintering method nanoparticles are developed.Sol-gel procedure is an economically feasible method with the following advantages. The disadvantages are also included in the following Table 2:
Microemulsion Method
The term microemulsion was first coined by Schulman et al. in 1959 [12]. By this technique inorganic nanomaterials including metal, semiconducting metal sulphite, metal salt, metal oxide, magnetic and composite nanoparticles are synthesized. Microemulsion is nothing but a stable, transparent, homogeneous,
isotropic dispersion with three phases in it i.e., polar phase (usually water), non-polar phase (usually hydrocarbon liquid/oil) and surfactant phase [13].
The general characteristics of this type of synthesis method are as follows:
The surfactant phase produces an inter-separation layer that stays between the aqueous and organic phase that reduces the interfacial tension and prevents coalescence of the droplets.Microemulsion leads to the development of nanoparticles that are oil-in-water or water-in-oil depending upon the surfactants used.Following are the synthesis method of nanoparticle [14]:
There are generally two routes of synthesis of nanoparticle: (1) One micro-emulsion method and the (2) Two microemulsion method.The first one is further divided into two types. The first one is the energy triggering method that requires a triggering agent to initiate the nucleation reaction in the precursor and the other method is microemulsion plus reactant method that is initiated by adding any one reactant into the microemulsion.In the latter method, two reactants are mixed together and the Brownian motion helps them to result in inter-micellar collisions and this leads to the mixing of the micellar components [15].Nucleation process within these micelle leads to the formation of nanoparticles.Following are the advantages and disadvantages of the microemlsion method for the preparation of nanoparticles (Table 3):
Hydrothermal Technique
The term ‘hydrothermal’ was first coined by British geologist Roderick Murchison (1792–1871). This technique is used to fabricate nanoparticles of iron oxide, metal oxide and lithium iron phosphate, etc.A huge amount of nanoparticles can be synthesized by this method that is optimum in size, morphology and surface chemistry [16].
Following are the characteristics of the nanoparticle that are developed by this method:
By this method, certain nanoparticles are successfully developed that are important solids, such as superionic conductors, microporous crystals, electronically conducting solids, chemical sensing oxides, magnetic materials, complex oxide ceramic and fluorides, and luminescence phosphors.This method can lead to the fabrication of nanoparticles, thin films, gels, distinguished helical and chiral structures, and particularly stacking-sequence materials.Nanoparticles are produced from a colloidal system that comprises of two or more phases that are solid, liquid or gas states and matter e.g. gels and foams mixed together under controlled temperature and pressure.Following are the synthesis method:
Synthesis can be done by batch hydrothermal or continuous hydrothermal process.The former procedure can be carried out by a system with the desired ratio phases while the latter carry out a higher rate of reaction in a shorter period of time [17].The advantages and disadvantages are as follows (Table 4):
Polyol Synthesis
Polyol method is a strategy to synthesis nanoparticles with controlled size, shape and composition. It is a widely used method for the synthesis of wide range of metal based, magnetic, metal oxide and metal hybrid nanoparticles [18].
