Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots

Abstract

A full understanding of the pharmacokinetic parameters describing nanomaterial disposition in the body would greatly facilitate development of a firm foundation upon which risk assessment could be based. This review focuses on the disposition of carbon based fullerenes and nanotubes, as well as quantum dots (QD) after parenteral administration to primarily rodents. The common theme across all particle types is that a major determinant of nanomaterial disposition is the degree of interaction with the reticuloendothelial (RE) cell system. Small water-soluble particles evading this system may be excreted by the kidney. Larger particles and those with the proper surface charge may get targeted to RE cells in the liver, spleen and other organs. Most nanomaterial kinetics are characterized by relatively short blood half-lives reflecting tissue extraction and not by clearance from the body. In fact, another common attribute to nanomaterial kinetics is retention of particles in the body. Finally, unlike many small organic drugs, nanomaterials may preferentially be trafficked in the body via the lymphatic system that has obvious immunological implications . T he technological and biomedical advancements inherent to the application of nanomaterials are becoming increasingly evident. In the field of medical applications, a thorough understanding of their pharmacokinetic properties is crucial for their safe and efficacious application. From the perspective of characterizing potential adverse effects, these data are also required for quantitative risk assessments to define the toxicology of the material. Pharmacokinetics is defined as the science of quantifying the rate and extent of the absorption, distribution, metabolism and elimination (ADME) of chemicals and drugs in the body using mathematical modeling approaches. The aim of pharmacokinetics is to relate drug dose or chemical exposure to biological effect. Pharmacokinetics has developed distinct sets of models and parameters which have been useful to describe and predict drug and chemical disposition, and also have specific

Toxico-/biokinetics of nanomaterials

“…They are absorbed in local lymphatic vessels from where they move to regional lymph nodes and enter via the thoracic duct into the systemic blood circulation. An important toxicological implication of this is that thereby NM have the potential to interact with the immune system in lymph nodes (Rivière 2009). …”

Frameworks and tools for risk assessment of manufactured nanomaterials

“…Kinetic tools for estimation of human internal exposure. Computational physiologically-based pharmacokinetic (PBPK) models can incorporate toxicokinetic data along with species-specific physiological properties to study the post-exposure absorption, distribution, metabolism and excretion (ADME) of MNs (Lee et al, 2009, Riviere, 2009, Lankveld et al, 2010, Van Kesteren et al, 2014. Specific PBPK tools were proposed by Lee et al (2009) for quantum dots, by Lankveld et al (2010) for nano Ag, and by Van Kesteren et al (2014) for nano SiO 2 .…”

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

“…24 Most absorption studies on ZnO nanoparticles evaluate biokinetics after a single-or repeated-dose oral exposure, since oral administration generally decreases bioavailability due to gastrointestinal barriers, the firstpass effect, and incomplete absorption related to liver and gut-wall functions. On the other hand, intravenously injected nanomaterials directly enter the systemic circulation, and thus in principle obtain 100% bioavailability.…”