Research Strategies for Safety Evaluation of Nanomaterials, Part V: Role of Dissolution in Biological Fate and Effects of Nanoscale Particles

TLDR

Dissolution, translocation, and disposition govern the fate and effects of inhaled particles, and at the nanoscale these processes are influenced by surface area, morphology, energy, aggregation, and leaching, yet dose metrics and dissolution–translocation relationships remain poorly defined. The review aims to establish a foundation for developing dissolution assays for nanoscale particles by integrating particle toxicology, material science, and analytical chemistry. Analytical methods such as chemical assays and particle characterization are used to assess dissolution and translocation, and the review proposes a framework combining these techniques to develop relevant dissolution assays for nanoscale particles.

Abstract

Dissolution, translocation, and disposition have been shown to play a key role in the fate and effects of inhaled particles and fibers. Concepts that have been applied in the micron size range may be usefully applied to the nanoscale range, but new challenges are presented based on the small size and possible change in the dissolution:translocation relationship. The size of the component molecule itself may be on the nanoscale. Solute concentration, surface area, surface morphology, surface energy, dissolution layer properties, adsorbing species, and aggregation are relevant parameters in considering dissolution at the nanoscale. With regard to the etiopathology caused by these types of particulates, the metrics of dose (particle number, surface area, mass or shape) is not yet well defined. Analytical procedures for assessing dissolution and translocation include chemical assay and particle characterization. Leaching of substituents from particle surfaces may also be important. Compartmentalization within the respiratory tract may add another dimension of complexity. Dissolution may be a critical step for some nanoscale materials in determining fate in the environment and within the body. This review, combining aspects of particle toxicology, material science, and analytical chemistry, is intended to provide a useful basis for developing relevant dissolution assay(s) for nanoscale particles.