**1. Introduction**

[160] Longmire M, Choyke PL, Kobayashi H. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine (Lond)

[161] Harper SL, Carriere JL, Miller JM, Hutchison JE, Maddux BL, Tanguay RL. Systemat‐ ic evaluation of nanomaterial toxicity: utility of standardized materials and rapid as‐

[162] Pompa P, Vecchio G, Galeone A, Brunetti V, Sabella S, Maiorano G, Falqui A, Bertoni G, Cingolani R. In Vivo toxicity assessment of gold nanoparticles in Drosophila mela‐

2008;3(5): 703-717.

154 Application of Nanotechnology in Drug Delivery

says. ACS Nano 2011;5(6): 4688-4697.

nogaster. Nano Research 2011;4(4): 405-413.

The chemotherapy of infections caused by bacteria that inhabit intracellularly presents a number of uncommon challenges. Many bacteria have found the way to produce a "silent" infection inside the cells and to avoid from their bactericidal mechanisms. However many methods for diagnosing and treating these and other bacterial infections presently exist, there is an essential need for new and improved approaches for bacterial destruction. Although the therapeutic efficacy of drugs has been well recognized, inefficient delivery could result in insufficient therapeutic index. It is now clear that a nanotechnology-driven approach using nanoparticles to selectively target and destroy pathogenic bacteria can be successfully implemented. Nanotechnology is one approach to overcome challenges of conventional drug delivery systems based on the development and fabrication of nanostructures. Some chal‐ lenges associated with the technology are as it relates to drug effectiveness, toxicity, stability, pharmacokinetics and drug regulatory control. Localized diseases such as infection and inflammation not only have perforated vasculature but also overexpress some epitopes or receptors that can be used as targets. Thus, nanomedicines can also be actively targeted to these locations. Various types of nanoparticulate systems have been tried as potential drug delivery systems, containing biodegradable polymeric nanoparticles, polymeric micelles, nanocap‐ sules, nanogels, fullerenes, solid lipid nanoparticles (SLN), nanoliposomes, dendrimers, metal nanoparticles and quantum dots. Nanoparticles have been found useful in the development of systemic, oral, pulmonary, transdermal and other administration routes to study drug targeting, the enhancement of drug bioavailability and protection of drug bioactivity and stability. In recent years, encapsulation of antimicrobial drugs in nanoparticle systems has emerged as an innovative and promising alternative that enhances therapeutic effectiveness

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and minimizes the undesirable side effects of drugs. The major goals in designing nanoparti‐ cles as delivery systems are to control particle size, surface properties and release of pharma‐ cologically active agents in order to achieve the site-specific action at the therapeutically optimal rate and dose regimen. This chapter focuses on nanoparticle-based drug delivery systems and clinical applications to treat a variety of bacterial infectious diseases and their potential applications in the field of medicine and biology.

pathogens utilize any portal of entry provided a satisfactory fluid medium be recognized at the site of lesion [4]. Extracellular pathogens utilize virulence mechanisms to avoid the antimicrobial capabilities of humoral immunity and phagocytosis thus advancing extracellular reproduction [8], in contrast with intracellular pathogens that promote the entry in to host cells

Nanoparticle based Drug Delivery Systems for Treatment of Infectious Diseases

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Classical examples of intracellular pathogens are *Brucella abortus*, *Listeria monocytogenes*, *Mycobacterium tuberculosis*, *Salmonella enterica*, and typical infectious diseases caused by them include brucellosis, listeriosis, tuberculosis, and salmonellosis [10]. Intracellular pathogenic bacteria have the ability to establish a relationship in the sensitive host which includes a stage of intracellular reproduction [11]. To establish an infection, these pathogens have to make contact with the appropriated type of host cell that provides suitable intracellular conditions for growth [4]. Bacteria such as *Mycobacterium, Legionella, Brucella* or *Listeria* have extended the ability to resist and replicate inside various mammalian cells including the aggressive phagocytic cells, which establish the first-line defense against invading pathogens [12].

The hydrophilic nature of some antibiotics prevents thier capacity to penetrate the cells and, furthermore, the internalized molecules are mostly accumulated in lysosomes, where the bioactivity of the drug is low. Therefore, limited intracellular activity against sensitive bacteria is often found [13, 14]. Thus, the use of drug delivery systems (DDS) has been suggested for passive targeting of infected cells of the mononuclear phagocytic system to enhance the therapeutic index of antimicrobials in the intracellular environment, while minimizing the side effects associated with the systemic administration of the antibiotic [15]. The pathophysiolog‐ ical and anatomical changes of the affected tissues in a disease state offer many possibilities for the delivery of various nanotechnology-based products [16]. Bacteria gains antibiotic resistance due to three reasons namely: 1) modification of active site of the target resulting in reduction in the efficiency of binding of the drug, 2) direct destruction or modification of the antibiotic by enzymes produced by the organism or, 3) efflux of antibiotic from the cell [17]. Nanoparticles (NPs) can target antimicrobial agents to the site of infection, so that higher doses of drug can be given at the infected site, thereby overcoming existing resistance mechanisms with fewer harmful effects upon the patient [18]. As with nanoparticles targeting intracellular bacteria, nanoparticles targeting the site of infection can release high concentrations of antimicrobial drugs at the site of infection, while keeping the total dose of drug administered low. Nanoparticles can be targeted to sites of infection passively or actively. Passively targeted nanoparticles selectively undergo extravasation at sites of infection, where inflammation has led to enhanced blood vessel porousness. Actively targeted nanoparticles contain ligands (e.g. antibodies) that bind receptors (e.g. antigens) at sites of infection [19]. Passive targeting with nanoparticles, however, faces multiple barriers on the way to their target; these include

containing macrophages and non-professional phagocytes such as epithelial cells [9].

**4. Targeted therapy of infections using nanoparticles**

**3.2. Intracellular pathogens**
