Evaluation of Biodistribution, Toxicology, and Toxicologic Pathology of Nanomaterials Used to Deliver Nucleic Acids

Abstract

The evaluation of the biodistribution and toxicology, including toxicologic pathology, of any therapeutic candidate is performed as an essential part of its development and, ultimately, its translation into the clinic. The research-based optimization and preclinical development of therapeutics delivered with nanoparticles (NPS) have been the subject of immense effort generating large numbers of publications but leading to relatively few actual applications. The principal reason for this is that this particular bench to bedside translation is fraught with numerous and variable scientific challenges. While in vitro screening may play a significant role in early development of many types of pharmaceuticals in the case of NPS, much of the burden falls on understanding the linkage between biodistribution, toxicology, and toxicologic pathology by emphasizing in vivo evaluation. Hence, the goal of this review is to better understand the current issues facing the early to late preclinical evaluation of various NPS by focusing on those being developed as nucleic acid carriers with the intent of eventually translating them into the clinic. While the emphasis will be on evaluation of NPS designated for delivery of nucleic acids, the basic principles can apply to NPS being developed for other medical uses.