Chapter 43 - Nanoparticulates

Abstract

This chapter describes the toxicologic pathology of nanoparticulates, the tools which can help toxicologic pathologists evaluate nanoparticulate studies, and emphasizes unique features occurring in nanoscale dimensions. Nanoparticulates are particulates with at least one dimension less than 100nm. The number and complexity of nanoparticulates is rapidly increasing due to improvements in nanotechnology, the technology that allows engineering in the nanoscale, and often from the atom up. Many products are in current use for diverse commercial purposes, with an estimated economic impact expanding into trillions of dollars in the near future. Recently, nanotechnology has expanded to include medical products, and the new products of nanomedicine include nanopharmaceuticals. Nanotoxicology, the study of the toxic effects of the new products of nanotechnology, lags far behind developments in nanotechnology and nanomedicine. Even fewer studies have investigated the toxicologic pathology of the products of nanotechnology. Nanoparticulates are generally more toxic on a mass basis than larger particles with the same composition. Nanoscaling of particulates increases surface area and thereby increases the dissolution rate of soluble particulates and increases inflammation associated with poorly soluble particulates. Nanosizing also facilitates movement between tissues and across intracellular barriers. In particular, nanoscaling permits extracellular transport in lymphatics, retrograde neuronal transport, and the use of nanoscale endocytic pathways for cell entry and intracellular transport. NPs are similar in size to subcellular structures, including components of the mitotic spindle, permitting critical interactions with these subcellular structures that are not possible with larger particulates. However, some of these unique features can be harnessed for new therapeutic and diagnostic products that allow targeted drug delivery and advanced imaging. Toxicologic pathologists will increasingly evaluate the safety of these new products of nanotechnology. An understanding of the toxicologic pathology of nanoparticulates plays a critical role in the safe development of nanotechnology.