ABSTRACT
Nanotechnology offers great potential benefits for drug delivery and therapy of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. Nanoparticles (NPs) have been of great interest for some time as they can be designed to simultaneously carry a drug payload, specifically target features of diseased tissues, and carry an imaging molecule to track drug accumulation and clearance in tissues. Moreover, they can be engineered for more sustained drug delivery to improve pharmacokinetics. A variety of NPs have been investigated in experimental animal models as tools to improve the therapeutic
efficacy of drugs or genes delivered to the lung or other organ systems [1]. The nanotechnology platform for drug delivery contains a number of very different types of nanostructures with widely varying properties, including dendrimers, fullerenes, carbon nanotubes (CNTs), and polymeric NPs. While nano-based drug delivery systems offer the potential for improved the efficacy of treatment, there are also potential risks associated with these novel therapeutic strategies [2]. Engineered NPs are desirable because they easily enter cells and they can be designed to interact with specific cellular structures (e.g., receptors) to allow for accumulation within specific regions of the cell. NPs can also be designed as pH-labile structures so that they degrade within the more acidic microenvironment of the cell to release drug payloads. Biocompatible NPs that are used for drug delivery, such as poly-(ethylene glycol)-block-lactide/glycolide copolymer (PEG-PLGA) NPs, generally have low toxicity but often do not persist in tissues long enough for sustained drug or gene payload delivery. Nevertheless, PEG-PLGA NPs might be useful for delivering metabolic inhibitors of inflammation for the treatment of pulmonary hypertension [3]. CNTs are durable and persist in biological systems for weeks or longer. Moreover, their tube-or fiberlike structure allows for extensive functionalization and loading of cargo. The versatile physicochemical features of CNTs allow for covalent and noncovalent functionalization to simultaneously carry several agents: (1) a drug, (2) an imaging agent (to track the course of delivery), and (3) a specific targeting agent (e.g., the antibody selective for the diseased tissue) [4]. Despite the potential benefits of CNTs for drug delivery, some of the same unique properties that make CNTs desirable for therapeutic applications also make them potentially toxic. Thus, despite potential therapeutic value for certain diseases, the toxic effects of CNTs might ultimately outweigh any beneficial effects as drug delivery systems. While no information yet exists on the adverse effects of CNTs in humans, growing evidence from in vivo exposure studies with rodents and in vitro cell culture models demonstrates that CNTs cause numerous adverse effects, including lung fibrosis, exacerbation of preexisting lung disease, adverse immune reactions, and DNA damage. The aims of this chapter is to provide an overview of some of the evidence that shows that CNTs have potential adverse health effects and analyze why CNTs should be carefully evaluated and designed if they are to be pursued further as drug delivery platforms.
