Design of Nanostructures for Versatile Therapeutic Applications

Alexandru Mihai Grumezescu

• Publisher: William Andrew
• Year: 2018
• Print ISBN: 9780128136676
• eBook ISBN: 9780128136683
• Topic: Scienze fisiche
• Subtopic: Nanoscienze

Design of Nanostructures for Versatile Therapeutic Applications focuses on antimicrobial, antioxidant and nutraceutical applications of nanostructured materials. Many books discuss these subjects, but not from a pharmaceutical point-of-view. This book covers novel approaches related to the modulation of microbial biofilms, antimicrobial therapy and encapsulate polyphenols as antioxidants. Written by an internationally diverse group of academics, this book is an important reference resource for researchers, both in biomaterials science and the pharmaceutical industry.- Assesses the most recently developed nanostructures that have potential antimicrobial properties, explaining their novel mechanical aspects- Shows how nanoantibiotics can be used to more effectively treat disease- Provides a cogent summary of recent developments in nanoantimicrobial discovery, allowing readers to quickly familiarize themselves with the topic

Chapter 1

Nanotechnology and Parkinson’s disease

Ioannis N. Mavridis^1,2, Maria Meliou^1,3, Efstratios-Stylianos Pyrgelis^1,4 and Eleni Agapiou^1,5, ¹‘C.N.S. Alliance’ Research Group, Athens, Greece, ²‘K.A.T.-N.R.C.’ General Hospital of Attica, Athens, Greece, ³‘Sotiria’ General Hospital of Chest Diseases, Athens, Greece, ⁴University of Athens School of Medicine, ‘Eginition’ Hospital, Athens, Greece, ⁵‘Asklepieio Voulas’ General Hospital, Athens, Greece

Abstract

The purpose of this chapter is to explore the role of nanotechnology in Parkinson’s disease. Nanomaterials can be engineered to cross the blood–brain barrier, to target specific cells and molecules and to act as vehicles for drugs, enhancing their therapeutic efficacy and/or bioavailability. Nanotechnology has contributed significantly to the study of the pathogenesis of Parkinson’s disease. Nanoparticles can be used for early imaging of neuronal loss and nanodevices can help in the detection/quantification of amyloid peptides in cerebrospinal fluid. Nanomaterials have been studied in experimental models of Parkinson’s for the administration of antiparkinsonian agents, neurotrophic factors, antioxidants, neuroprotective and antiapoptotic factors. Nanotechnology-enabled naso-brain drug delivery, viral vectors, gene nanocarriers and exhaled breath analysis with nanoarray are other examples of nanotechnology applications. Nanotoxicity, however, is a realistic problem in mice and requires further investigation. In conclusion, nanotechnology has several applications potentially useful in the diagnosis and management of Parkinson’s disease patients.

Keywords

Antiparkinsonian agents; α-synuclein; dopaminergic neurons; nanomaterials; nanomedicine; nanotechnology; nanotoxicity; neurodegeneration; Parkinson’s disease

Chapter Outline

• 1.1 Introduction 1
  • 1.1.1 Parkinson’s Disease 1
  • 1.1.2 Nanotechnology 3
  • 1.1.3 Nanomedicine 3
  • 1.1.4 Purpose 4
• 1.2 Genetic and Molecular Mechanisms of Parkinson’s Disease 5
  • 1.2.1 Molecular Mechanisms 5
  • 1.2.2 Genetics 7
• 1.3 Nanotechnology and Parkinson’s Disease 8
  • 1.3.1 Pathogenesis of Parkinson’s Disease 8
  • 1.3.2 Diagnostic Methods for Parkinson’s Disease 10
  • 1.3.3 Management of Parkinson’s Disease 12
• 1.4 Nanotoxicity 21
• 1.5 Conclusions 22
• References 24
• Further Reading 28

1.1 Introduction

1.1.1 Parkinson’s Disease

Parkinson’s disease is a common, multifactoral, progressive, neurodegenerative disorder characterized by a protein fibrillation process and loss of dopaminergic neurons in the basal ganglia. This is mainly due to an abnormal accumulation of α-synuclein in intraneuronal Lewy bodies in the substantia nigra, which leads to subsequent loss of dopamine in the midbrain region (Busquets et al., 2015; Ganesan et al., 2015; Linazasoro, 2008; Majidinia et al., 2016; Mohanraj et al., 2013). This causes an imbalance of neurotransmitters, such as dopamine and acetylcholine, leading primarily to impairment of voluntary and controlled movements (Ganesan et al., 2015; Majidinia et al., 2016). Although not exclusive, the involvement of the dopaminergic system is the most prominent in Parkinson’s disease (Linazasoro, 2008), which is the second most common neurodegenerative disorder worldwide after Alzheimer’s disease (Majidinia et al., 2016).

Parkinson’s disease is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta projecting to the striatum (Zhao et al., 2014). The striatum, the first relay of the basal ganglia system, is critically involved in motor functions and motivational processes. The dorsal striatum is fundamental to motor control and motor learning, whereas ventral striatum, especially the nucleus accumbens, is essential for the reward system, motivation, and reinforcement by drugs. This system is dysfunctional in Parkinson’s disease. With disease progression, beside dopaminergic degeneration, nondopaminergic nuclei (such as the locus coeruleus, the nucleus basalis of Meynert and the dorsal raphe) are affected (Mavridis, 2015).

The clinical symptoms usually appear late in the course of the disease, after more than 60% of the dopaminergic neurons are lost (Kumar et al., 2010). There is a great variety of clinical manifestations among patients related to the balancing effects of compensatory mechanisms, the effects of additional pathologies, the degree of anatomic damage and the constant change of neurotransmission system, especially when Parkinson’s disease is medically treated (Linazasoro, 2008). These manifestations include motor and nonmotor symptoms, resulting in severe disability (Kumar et al., 2010). The major motor symptoms include tremor, speech and writing changes, decelerated movement and muscle rigidity (Ganesan et al., 2015). Nonmotor manifestations include cognitive, behavioral, and autonomic symptoms. Neuropsychiatric symptoms occur in the majority of patients and should be considered as an integral part of the disease. These include dementia and cognitive impairment, depression, dysthymia, anxiety disorders, psychosis, apathy, sleep disorders, sexual disorders, and treatment-related psychiatric symptoms. Neuropsychiatric symptoms are important determinants of mortality, disease progression, and patients’ and caregivers’ quality of life (Mavridis, 2015).

Management of Parkinson’s patients includes neuroprotective or disease-modifying therapies, symptomatic treatment, and surgical interventions. Neuroprotective approaches are based on “attacking” pathological mechanisms such as oxidative stress, mitochondrial dysfunction, excitotoxicity, caspase activation, apoptosis, inflammation, and trophin deficiency. Many types of medications are available for the symptomatic treatment of Parkinson’s disease, including anticholinergics, amantadine, L-dopa (L-3,4-dihydroxyphenylalanine or levodopa), monoamine oxidase inhibitors, catechol-O-methyltransferase inhibitors, and dopamine agonists. Surgical management primarily includes deep brain stimulation (DBS) of targets such as the subthalamic nucleus, the internal segment of the globus pallidus, and thalamic nuclei (Jankovic, 2016).

Parkinson’s disease incidence is higher among patients older than 65 years. The continuing aging of populations results in a continuously increasing presence of neurodegenerative disorders. Current treatments of neurodegenerative disorders, which only delay progression and complications during the course of these diseases, cost nearly $20,000,000,000 in the United States of America; a cost that increases every year (Kumar et al., 2010). The socio-economic effects of this phenomenon, call for more efficient methods of diagnosis and treatment of these disorders (Giordano et al., 2011). The expected increase in lifespan of the global population will further lead to a rise in age-related diseases, including neurodegenerative disorders.

1.1.2 Nanotechnology

Nanotechnology uses engineered and appropriately manipulated materials (nanomaterials) that interact with biological systems at a molecular level. According to the National Nanotechnology Initiative, nanotechnology is defined as the manipulation of matters with at least one dimension sized between 1 and 100 nm (Stern and Johnson, 2008). Molecular nanotechnology is an engineering discipline with the goal to build devices and structures that have every atom in the proper place (Kaehler, 1994). This technology has a broad range of research and applications in many fields, including medicine (Stern and Johnson, 2008). In general, nanotechnology allows for an intervention at a molecular level and any desired cellular signaling pathway can be targeted (Linazasoro, 2008). It provides scientists with the potential to interact with various biological systems by stimulating, responding to, and interacting with molecular target sites in order to induce responses, while theoretically minimizing side effects (Modi et al., 2010).

Today, nanotechnology and nanoscience approaches to particle design and formulation are beginning to expand the market for many drugs and are forming the basis for a highly profitable niche within the industry. Nanoscale vehicles and entities can be used, for example, for site-specific drug delivery and medical imaging after parenteral administration. However, some predicted benefits of nanotechnology may be overestimated (Moghimi et al., 2005).

1.1.3 Nanomedicine

Applications of nanotechnology for treatment, diagnosis, monitoring and control of biological systems have been referred to as nanomedicine by the National Institutes of Health (Moghimi et al., 2005). Accordingly, nanomedicine is the process of diagnosing, treating, and preventing disease and traumatic injury, of relieving pain, and of preserving and improving human health, using molecular tools and molecular knowledge of the human body (Freitas, 2005b). In fewer words, nanomedicine is the applications of nanotechnology to the medical field (Stern and Johnson, 2008).

The early genesis of the concept of nanomedicine sprang from the visionary idea that tiny nanorobots and related machines could be designed, manufactured, and introduced into the human body, to perform cellular repairs at a molecular level. Nanomedicine today has branched out in hundreds of different directions, each of them embodying the key insight that the ability to structure materials and devices at a molecular scale can bring enormous immediate benefits in the research and practice of modern medicine (Freitas, 2005a).

The implementation of nanotechnology for medical purposes includes the production of biomedical devices, nanoelectronic biosensors and drug delivery systems. Nanomedicine is a developing field of research and is expected to offer new insight into the study and treatment of various disorders (Andressen and Wree, 2013; Giordano et al., 2011; Mazza et al., 2013). Several types of nanomaterials, with different features, are currently available for medical use (Re et al., 2012). Nanoparticles used in nanomedicine include solid colloidal matrix-like particles made of polymers or lipids. They are mainly administered intravenously and they have been developed for targeted delivery of therapeutic or imaging agents (Linazasoro, 2008).

In the relatively near future, nanomedicine can address many important medical problems by using nanoscale-structured materials and simple nanodevices that can be manufactured today, including the interaction of nanostructured materials with biological systems (Freitas, 2005b). Research into the rational delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents is at the forefront of projects in nanomedicine. These involve the identification of precise targets (cells and receptors) related to specific clinical conditions and the choice of appropriate nanocarriers to achieve the required response, while minimizing side effects. Mononuclear phagocytes, dendritic cells, endothelial cells, and cancer cells (of the tumor or its neovasculature) are key targets (Moghimi et al., 2005). In the mid-term, biotechnology will make possible even more remarkable advances in molecular medicine and biobotics, including microbiological biorobots or engineered organisms. In the longer term, the earliest molecular machine systems and nanorobots may join the medical armamentarium, finally giving physicians the most potent t...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Series Preface: Pharmaceutical Nanotechnology
• Preface
• Chapter 1. Nanotechnology and Parkinson’s disease
• Chapter 2. Stem cell and gene-based approaches for cardiac repair
• Chapter 3. Nanostructured lipid carriers: Revolutionizing skin care and topical therapeutics
• Chapter 4. Nanotechnology for ocular drug delivery
• Chapter 5. Polymeric nanoparticles and sponges in the control and stagnation of bleeding and wound healing
• Chapter 6. Nanotechnology approaches to pulmonary drug delivery: Targeted delivery of small molecule and gene-based therapeutics to the lung
• Chapter 7. Brain targeting with lipidic nanocarriers
• Chapter 8. Nanotechnological approaches to colon-specific drug delivery for modulating the quorum sensing of gut-associated pathogens
• Chapter 9. Psoriasis vulgaris—Pathophysiology of the disease and its classical treatment versus new drug delivery systems
• Chapter 10. Getting under the skin: Cyclodextrin inclusion for the controlled delivery of active substances to the dermis
• Chapter 11. Preparation of high-valence bifunctional silver nanoparticles for wound-healing applications
• Chapter 12. Metal nanoparticles as potent antimicrobial nanomachetes with an emphasis on nanogold and nanosilver
• Chapter 13. Modulation of microbial quorum sensing: Nanotechnological approaches
• Chapter 14. Lipid-based colloidal carriers for topical application of antiviral drugs
• Chapter 15. Encapsulation of pharmaceutically active dietary polyphenols in cyclodextrin-based nanovehicles: Insights from spectroscopic studies
• Index