Biological and intracellular fates of drug nanocrystals through different delivery routes: Recent development enabled by bioimaging and PK modeling.

Nanocrystals have contributed to exciting improvements in the delivery of poorly water-soluble drugs. The biological and intracellular fates of nanocrystals are currently under debate. Due to the remarkable commercial success in enhancing oral bioavailability, nanocrystals have originally been regarded as a simple formulation approach to enhance dissolution. However, the latest findings from novel bioimaging tools lead to an expanded view. Intact nanocrystals may offer long-term durability in the body and offer drug delivery capabilities like those of other nano-carriers. This review renews the understanding of the biological fates of nanocrystals administered via oral, intravenous, and parenteral (e.g., dermal, ocular, and pulmonary) routes. The intracellular pathways and dissolution kinetics of nanocrystals are explored. Additionally, the future trends for in vitro and in vivo quantification of nanocrystals, as well as factors impacting the biological and intracellular fates of nanocrystals are discussed. In conclusion, nanocrystals present a promising and underexplored therapeutic opportunity with immense potential.