ABSTRACT
Figure 1.1 (a) Importance of nanomedicine risk versus benefit and (b) papers published per year, as listed in PUBMED when searched using the descriptors shown.
scientific disciplines keen to exploit advances in nanoscience to develop novel nanotechnologies for medical applications, that is, for “nanomedicine” [1, 3]. In parallel, there has been a growing realization that “ultrafine” nanoparticles in the environment and/or the workplace are particularly hazardous during prolonged accidental human exposure [4]. This fact, together with the increasing use of nanomaterials in a broad range of applications (from construction to aerospace materials, from environmental applications and electronic components to cosmetics and consumer products, etc.), has led to the birth of the field now termed “nanotoxicology” [4-6], which is overviewed elsewhere in this volume. Although the number of publications using the descriptors either “nanomedicine” or “nanotoxicology” has increased rapidly over the last decade (Fig. 1.1b), compared to the terms “nanoparticles” (first used in pharmaceutical sciences since the 1970s) and “nanomaterials” (first used in materials science since the 1980s) and “ultrafine particle toxicology” (used since the 1980s), the number of papers published is still significantly lower. It important to be aware of all current and historical literature relating to the toxicological properties of nanosized materials in relation to environmental, accidental human, and purposeful (nanomedicines) human exposure. For the reader new to the area of “nanomedicine(s)” it is also important to point out that the overall field of nanomedicine encompasses many different potential healthcare applications of nanotechnologies: (i) Diagnostics, devices/biosensors, and surgical tools usually
used outside the patient (ii) Diagnostics and theranostics (a combination of therapeutic and diagnostic functions) designed for patient administration (iii) Nanostructured biomaterials (often combined with cell therapy) for in vitro or in-patient biomedical applications (iv) Nanomedicines (sometimes called nanopharmaceuticals) given to patients by a variety of routes of administration (includes also diagnostics)
This chapter focuses on the safety issues relating to nanomedicines/nanopharmaceuticals. Nanomedicines include inherently active therapeutics, advanced drug delivery systems (e.g., for low-molecular-weight drugs, proteins, genes, aptamers, and small interfering RNA [siRNA]), and vaccine delivery systems (discussed in Ref. [1]). They are often hybrid multicomponent, nanosized structures, and there is growing ambition to combine diagnostic and therapeutic capacity in a single system, that is, to create what has been termed a nanotheranostic. All nanomedicines are carefully designed to exhibit therapeutic benefit against a particular disease (stage of the disease) in a particular patient population using a particular route for administration. They are carefully engineered nanosized constructs in the 1-1000 nm size range and can be made using either top-down or bottom-up manufacturing techniques (discussed at length in Ref. [1]). Why the 1-1000 nm size range? The need for a scientifically justified, legally binding definition of a “nanomaterial” applicable for safety regulation across all sectors is evident. It has, however, quickly become apparent that it is difficult to find an overarching definition suitable to catch all nanomaterials (in relation to a specific size range having unique physicochemical/toxicology properties) or indeed could include all types of nanomedicines. Many scientific experts have acknowledged that none of the popular size demarcation thresholds (often 1-100 nm) are scientifically applicable across “all” nanomaterials [7]. Moreover it is agreed by many that “catch-all” size descriptors are more likely to create regulatory gaps rather than close them [8, 9]—a dangerous game in the context of nanomedicines. Although a large number of learned societies, governmental agencies, and also the International Organization for Standardization (ISO) have invested much committee time elaborating libraries of “nanodefinitions” (e.g., [10]), it is wise to embrace them with caution, as many proposed definitions are still viewed as controversial or simply wrong. The terminology used in this chapter is defined in Box 1.1.
