Kumar Nanotechnology and Nanomaterials in the Treatment of Life-threatening Diseases

1. Auflage 2013
ISBN: 978-0-323-26450-1
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 408 Seiten

Reihe: Micro and Nano Technologies

Nanotechnology and Nanomaterials in the Treatment of Life-threatening Diseases takes a scientific approach to nanotechnology and nanomaterials applications in medicine, while also explaining the core biological principles for an audience of biomedical engineers, materials scientists, pharmacologists, and medical diagnostic technicians. The book is structured by major disease groups, offering a practical, application-based focus for scientists, engineers, and clinicians alike. The spectrum of medical applications is explored, from diagnostics and imaging to drug delivery, monitoring, therapies, and disease prevention. It also focuses specifically on the synthesis of nanomaterials and their potential health risks (particularly toxicity). Nanomedicine - the application of nanomaterials and devices for addressing medical problems - has demonstrated great potential for enabling improved diagnosis, treatment, and monitoring of many serious illnesses, including cancer, cardiovascular and neurological disorders, HIV/AIDS, and diabetes, as well as many types of inflammatory and infectious diseases. - Gain an understanding of how nanotechnologies and nanomaterials can be deployed in the fight against the major life-threatening diseases: cancer, neurological disorders (including Alzheimer's and Parkinson's), cardiovascular diseases, and HIV/AIDS - Discover the latest developments in nanomedicine, from therapies and drug delivery to diagnostics and disease prevention - The authors cover the health risks of nanomaterials as well as their benefits, considering toxicity and potential carcinogens

Autoren/Hrsg.

Kumar, Narenda

Kumar, Rajiv

Leseproben

Chapter 2 Nano-based Drug Delivery and Diagnostic Systems
Abstract
The chapter on “Nano-based Drug Delivery and Diagnostic Systems” specifically describes the different types of nanomaterials i.e., inorganic, organic, polymeric, nanoscale metal-organic framework, etc., for drug delivery (which also include targeted and remotely triggered) systems together with specific nanopolymeric materials for the safe delivery of RNA/DNA; their pharmacokinetics and organ clearance. The size- and shape-dependent clearance of NPs from organs (liver, kidney, etc.) has been discussed together with biological components (biological fluids, phagosome, endosome, lysosome, protein enzymes, etc.). In addition, a separate section is devoted to the emerging molecular level as well as imaging diagnostics techniques using NPs as markers and contrast agents. Keywords
NPs-based drug delivery system; Pharmacokinetics; Organ clearance; Diagnostic imaging techniques; Contrast agents; Biomarkers 2.1 Introduction
Medical therapies have become more tailored to specific disease. The method by which a drug is delivered can have a significant effect on its efficacy. Some drugs have an optimum concentration range within which maximum benefit is derived and concentration above or below this range can be toxic or produces no therapeutic benefit at all. On the other hand, the very slow progress in the efficacy of the treatment of severe disease has suggested a growing need for a multidisciplinary approach to the delivery of therapeutics to targets in tissues. From this, new ideas were generated on controlling the pharmacokinetics, pharmacodynamics, nonspecific toxicity, immunogenicity, bio-recognition, and efficacy of drugs. These new strategies, often called drug delivery systems (DDS), are based on interdisciplinary approaches that combine polymer science, pharmaceutics, bioconjugated chemistry, and molecular biology [1]. Conventional methods of drug administration route include oral, transdermal, injection (iv), implants, etc. In general, a drug administration route, while incorporating an existing medicine into a new drug delivery system, can significantly improve its performance in terms of efficacy, safety, and improved patient compliance. The need for delivering drugs to patient efficiently and with fewer side effects has prompted scientists, in research institutes as well as pharmaceutical industries, to engage in the development of new drug delivery systems—laying special emphasis on multiple platform technologies. These technologies are focused to minimize drug degradation and loss, to prevent harmful side effects, and to increase drug bioavailability and the fraction of drug accumulated in the desired zone, various drug delivery and drug targeting systems are currently under development involving huge investment by pharmaceutical industries. Among the drug carriers include soluble polymers, microparticles made of insoluble or biodegradable natural and synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins, liposomes, and micelles. The carriers can be made slowly degradable, stimuli responsive (e.g. pH- or temperature sensitive), and even targeted (e.g. by conjugating them with specific antibodies against certain characteristic components of the area of interest). Targeting is defined as the ability to direct the drug-loaded system to the site of interest. Two major mechanisms can be distinguished for drug release: (i) passive and (ii) active targeting. As mentioned above, drugs can be administered to a patient by many delivery systems including oral, transdermal, injection, implant, etc. Most of the drugs are amenable to these systems. However, with the sequencing of the human genomes, biotechnology companies are rapidly developing a large number of peptides and protein-based drugs. It is expected that in the next 10 years, protein and peptides-based drugs will constitute half of the new drugs introduced into the market, and more than 80% of these protein drugs will be antibodies. Most of the pharmaceuticals (i.e. proteins, peptides, carbohydrates, oligonucleotides, and nucleic acid in the form of RNA and DNA) present a drug delivery challenge because these are often large molecules that rapidly degrade in the bloodstream, have limited ability to cross cell membrane barriers, and cannot be delivered orally. Such molecules are difficult to deliver via conventional routes. In the 21st century, the pharmaceutical industry is caught between the downward pressure on price and the increasing cost of successful drug discovery and development. The average cost and time for the development of a new chemical entity are much higher (approximately $500 million and 10–12 years) as compared to those required to develop a novel drug delivery system (NDDS) ($20–30 million and 3–4 years). Limited formularies, patent expiry with subsequent entry of generic competition, and vertical integration have led the entire pharmaceutical industry (approximately 350 drug delivery and 1000 medical devices companies) to focus on designing and developing new and better methods of drug delivery. The sale of drug delivery products was valued at more than $130 billion worldwide, in 2012. Both active and passive delivery systems are ideally designed to avoid nonspecific drug distribution throughout the body, to regulate drug release kinetics, to minimize side effects, and to improve the therapeutic efficacy compared to systemic applications of the corresponding drug. Fast drug release before reaching the targeted site may cause systemic side effects and a slow release may cause drug resistance in initially sensitive cells. In addition, in the treatment of some pathology, instead of having a sustained drug release, a pulsed release is desirable (i.e. pain, hormonal disorders, etc.). To meet diverse requirements and to overcome limitations of current imaging and drug delivery systems, nanotechnology is fast emerging as the technology for imaging as well as an alternative effective drug delivery system. Numerous nanoparticle-based drug formulations and diagnostic agents have already been developed, e.g. for the treatment of cancer, diabetes, pain, allergy (in particular, asthma), and infections [2]. Over recent years, rapid developments of nanoparticle-based drug delivery systems have facilitated the targeting of specific tissues. Nanomedicine has blossomed into a billion dollar industry because of these compounds’ inherent ability to overcome solubility and stability problems, localize drug delivery, as well as to diagnose via in vivo imaging. Coupled with genomic tailoring, nanomedicine may soon spawn the much anticipated personalized medicine. Upcoming innovations in nanomedicine may even generate multifunctional entities enabling simultaneous diagnosis, delivery of drugs, and monitoring the treatment [3]. In addition, the development of smart nano-artificial machines is fast emerging for integration into the body for targeted drug delivery [4,5]. 2.2 Nanoparticles-based drug delivery system
A number of nanoparticles-based drug carriers have been studied with success in recent years. These include dendrimers, micelles, emulsions, organic and inorganic micro- and nanoparticle systems, nanotubes, liposomes, viruses, metal-organic frameworks (MOFs), hydrogels, polyelectrolyte multilayers, etc. A comparison of these systems is given in Table 2.1, with specifics on nanoparticle size range, type of therapeutics carried, and specific advantages and limitation of each system [6–8]. Table 2.1 Comparison of Nanoparticle Drug Delivery Systems [7] Reproduced with Permission Many of these systems can be engineered to contain multiple tags (i.e. chromophores, optical or magnetic stimuli responsive nanoparticles, etc.) together with the carriers for both imaging/cell trafficking and therapeutic agents). Such approaches are expected to address drug delivery related issues such as on demand activation of molecular interactions, novel diffusion control devices, nanostructured “Smart” surfaces and materials, and prospects of coupling of drug delivery to sensors and implants. 2.2.1 Types of nanoparticles
2.2.1.1 Inorganic nanoparticles Ceramic nanoparticles are typically composed of inorganic compounds such as silica or alumina. However, the other nanoparticles such as metals [9], metal oxide [10], and metal sulfides [11] can also be used to produce a myriad of nanostructures with varying size, shape, and porosity. Generally, inorganic nanoparticles may be engineered to evade the reticuloendothelial system by varying size and surface composition [12]. Moreover, they may be made porous, and provide a physical encasement to protect an entrapped molecular payload from degradation or denaturation. Hollow silica nanoparticles have been prepared, with surface pores, leading to a central reservoir [13,14]. In contrast, mesoporous silica materials, containing a complex “worm-like” network of channels throughout the interior of the solid nanoparticles, MCM-41, reported in 1992, have been of great interest as a drug delivery system. In a study, when ibuprofen was introduced into the pores of these nanomaterials at a drug-to-MCM-41 weight ratio of approximately 3:7, as determined by thermo-gravimetry, these loaded MCM-41 particles were then subjected to a simulated body fluid and demonstrated to be potentially viable drug delivery systems. This work demonstrated that mesoporous silica...