Metal Nanoparticles for Drug Delivery and Diagnostic Applications

Muhammad Raza Shah,Muhammad Imran,Shafi Ullah

• Publisher: Elsevier
• Year: 2019
• ISBN:
  9780128169612
• Topic: Technology & Engineering
• Subtopic: Materials Science
• Index: Technology & Engineering

Metal Nanoparticles for Drug Delivery and Diagnostic Applications addresses the lifecycle of metal nanoparticles, from synthesis and characterization, to applications in drug delivery and targeting. It is an important resource for those in biomaterials, nanomedicine and pharmaceutical sciences, exploring gold, silver and iron-based drug delivery systems for controlled and targeted delivery of potential drugs and genes for enhanced clinical efficacy. Nanotechnology is widely used in drug delivery due to its ability to reduce plasma fluctuation of drugs, high solubility, and efficiency, the relatively low cost of nanoscale products, and enhancement of patient comfort, hence this resource is a welcome edition to the science.

• Illustrates the progression of nanoparticle therapeutics from basic research to applications
• Explores new opportunities and ideas for developing and improving technologies in nanomedicine and nanobiology
• Discusses the toxicity of different types of metal nanoparticles and how to ensure their safe use

Chapter 1

Metal nanoparticles toxicity: role of physicochemical aspects

Saeed Ahmad Khan, Department of Pharmacy, Kohat University of Science and Technology, Kohat, Pakistan

Abstract

Metal nanoparticles (NPs) have been focus of scientists’ interest for the last few decades owing to their huge potential in nanotechnology. The possibility of synthesis in different sizes, shapes, and with variety of surface modification allows metal NPs to be conjugated with antibodies, targeting ligands, and drugs, thus opening avenues for wide range of applications. However, with reference to toxicity there is a serious lack of knowledge about their influence on human health and environment. The physicochemical characteristics of metal NPs such as their shape, size, surface area, the presence or absence of specific active groups on the surface, the charge and composition are major determinants in the toxicity of NPs. In this chapter we intend to highlight the impact of physicochemical properties of metal NPs with respect to their toxicity.

Keywords

Drug delivery; nanotechnology; toxicology; article size; particle shape; surface properties

Contents

Outline

• 1.1 Introduction 1
• 1.2 Mechanisms of metallic nanoparticles toxicity 2
  • 1.2.1 Membrane damage 2
  • 1.2.2 Release of toxic dissolved species 2
  • 1.2.3 Reactive oxygen species generation 3
• 1.3 Effect of physicochemical properties on toxicity of metallic nanoparticles 3
  • 1.3.1 Effect of size 3
  • 1.3.2 Effect of surface charge 5
  • 1.3.3 Effect of shape 7
  • 1.3.4 Effect of solubility 8
• 1.4 Conclusion 9
• References 9

1.1 Introduction

Metallic nanoparticles (MNPs) have a metal core composed of inorganic metal or metal oxide that is usually covered with a shell made up of organic or inorganic material or metal oxide. Metal NPs have diverse application in our daily life (Table 1.1). The development of new economically feasible methods for production of MNPs have introduced pilot-scale production of MNPs, that have gained market in various consumer products such as creams, shampoos, clothing, footwear, and plastic containers (Diegoli et al., 2008).

Table 1.1

Some of the common MNPs and their applications.

Metals	Application of nanoparticles
Aluminum (Al)	Fuel additive/propellant, explosive, coating additive
Gold (Au)	Cellular imaging, photodynamic therapy
Iron (Fe)	Magnetic imaging, environmental remediation
Silica (Si)	Electric and thermal insulators, catalyst supports, drug carriers, gene delivery, adsorbents, molecular sieves and filler material
Silver (Ag)	Antimicrobial, photography, batteries, electrical
Copper (Cu)	Antimicrobial (i.e., antiviral, antibacterial, antifouling, antifungal), antibiotic treatment, alternatives, nanocomposite coating, catalyst, lubricants, inks, filler materials for enhanced conductivity and wear resistance
Cerium (Ce)	Polishing and computer chip manufacturing, fuel additive to decrease emissions
Manganese (Mn)	Batteries, catalyst
Nickel (Ni)	Conduction, magnetic properties, catalyst, battery manufacturing, printing inks
Titanium dioxide (Ti)	Photocatalyst, antibacterial coating, sterilization, paint, cosmetics, sunscreens
Zink (Zn)	Skin protection, sunscreen

Reproduced with permission from Schrand, A.M., Rahman, M.F., Hussain, S.M., Schlager, J.J., Smith, D.A., Syed, A.F., 2010. Metal-based nanoparticles and their toxicity assessment. Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol., 2, 544–568.

Though globally great advances have been made in the manufacturing and use of MNPs, there is still a great lack in the knowledge regarding the toxicity related impact of these on human health and environment (Schrand et al., 2010). Although there are some preliminary reports available on the inherent toxicity of some MNPs indicating that they can affect biological system at the cellular and subcellular level, however, extensive understanding of the basis of MNPs toxicity is required before large-scale production (Schrand et al., 2010).

1.2 Mechanisms of metallic nanoparticles toxicity

Different mechanisms are involved in causing cellular toxicity including physical damage, toxic ions release, and reactive oxygen species generation.

1.2.1 Membrane damage

The MNPs may cause acute toxic response directly at the cell membrane or by their cellular uptake. NPs possess several properties such as very high surface area and numerous morphologies (Klabunde et al., 1996). The nonspecific damage to cell membranes is mainly caused by the abrasive nature of MNPs, such as magnesium oxide NPs damaged bacterial cell membranes, and resulted in leakage of cell contents and ultimately cell death (Stoimenov et al., 2002). Other studies also reported bacterial cell membrane damage by silver and zinc oxide when used in high concentrations (Morones et al., 2005). The cell membrane damage is more pronounced in unicellular organisms (Wiesner et al., 2006).

1.2.2 Release of toxic dissolved species

The release of dissolved metal from the MNPs surface may exert toxic effects. A localized point source of high concentration is obtained with slowly dissolving NPs. As a result, cells in close proximity to the main point source have higher concentration of metal as compared to those in the bulk solution (Apte et al., 2009). Minute amounts of some metals can exhibit extreme toxicities. For instance copper and zinc in minute amounts can be extremely toxic to aquatic organisms (Santore et al., 2001). Other studies have also reported the rapid dissolution of ZnO and cytotoxicity of Zn⁺² on human mesothelioma and rodent fibroblast cell lines (Brunner et al., 2006).

1.2.3 Reactive oxygen species generation

MNPs have a great ability to generate reactive oxygen species (ROS) such as peroxides, oxygen ions, and free radicals due to their physicochemical attributes including large surface area to volume ratio and high chemical reactivity (Oberdörster et al., 2005). ROS can interact with cells via different mechanisms leading to oxidative stress. It may damage several intracellular organelles. Oxidative stress results in loss of function of the main components of the body, such as fats, proteins, nucleic acids, etc., that are prone to oxidation (Fahmy and Cormier, 2009). Some of the MNPs have the tendency to induce oxidative stress. The main reasons for generation of oxidative stress include: (1) the reactive surface of MNPs with prooxidant functional groups; (2) active redox cycling on the surface of MNPs due to transition metal-based NP; and (3) particle–cell interactions (Risom et al., 2005; Manke et al., 2013).

1.3 Effect of physicochemical properties on toxicity of metallic nanoparticles

Commercially, MNPs are prepared to impart certain physicochemical properties to the material that are relevant to the desired application. Given the diversity of products and their applications, one cannot generalize about the chemistry of MNPs. For inst...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of contributors
• Preface
• Chapter 1. Metal nanoparticles toxicity: role of physicochemical aspects
• Chapter 2. Erythrocytes modified (coated) gold nanoparticles for effective drug delivery
• Chapter 3. Biosynthesized metal nanoparticles as potential Alzheimer’s disease therapeutics
• Chapter 4. Gold nanoparticles in cancer diagnosis and therapy
• Chapter 5. Gold nanorods: new generation drug delivery platform
• Chapter 6. Surface engineered gold nanorods: intelligent delivery system for cancer therapy
• Chapter 7. Role of gold- and silver-based nanoparticles in stem cells differentiation
• Chapter 8. Nanosilver at the interface of biomedical applications, toxicology, and synthetic strategies
• Chapter 9. Silver nanoparticles: a promising nanoplatform for targeted delivery of therapeutics and optimized therapeutic efficacy
• Chapter 10. Bactericidal potentials of silver nanoparticles: novel aspects against multidrug resistance bacteria
• Chapter 11. Magnetic nanoparticles: drug delivery and bioimaging applications
• Chapter 12. Surface functionalized magnetic nanoparticles for targeted cancer therapy and diagnosis
• Chapter 13. Clinical implications of metals-based drug-delivery systems
• Chapter 14. pH-sensitive drug delivery systems
• Chapter 15. Ionic liquid–based colloidal nanoparticles: applications in organic synthesis
• Chapter 16. Biomedical applications of magnetic nanoparticles
• Index