ABSTRACT

Although not a topic of the present chapter, it is instructive to realize that some nanoparticle-protein interactions are not strictly pharmacokinetic but also impact pharmacodynamics. This is when the mechanism of action of the nanoparticle involves direct interaction with proteins responsible for disease (e.g., amyloid) in Alzheimer’s or Parkinson’s disease. As an example, one potential approach for modulating Alzheimer’s disease is to use specific nanomaterials that bind to blood-amyloid β protein in an effort to shift the blood-brain barrier equilibrium of this protein in favor of blood, which would reduce brain deposition and allow its removal from the body via the RES [22]. This is a pharmacokinetic property that determines a nanoparticle’s pharmacodynamic profile and supports the hypothesis stated in the first sentence of the present chapter on the dominance of pharmacokinetic properties to predict nanoparticle activity. The lymphatic system is where lipophilic particulate matter often transits the body yet is not normally accounted for in classic pharmacokinetic models. Intramuscular and subcutaneous injections of nanoparticles [23], as well as inhalational administration [5] and intradermal injections [24], may result in nanoparticle accumulation within the lymphatic system. In fact, QDs could be used to image lymphatic drainage to lymph nodes in surgery [25], a study that showed QDs between 15-20 nm tend to be retained in the first lymph node encountered. 8.2.3 EliminationThere are some aspects of a nanoparticle’s elimination and clearance from the body that are also different from what is encountered for small molecules. Studies using QDs of different sizes have suggested that only particles smaller than 5.5 nm are capable of being cleared by the kidney [26], the primary route from where most small molecules or their metabolites are excreted from the body. This is consistent with the kidney’s normal physiological role of not filtering plasma proteins or other formed elements in the blood. A lack of robust urinary or biliary secretion pathways for nanomaterials is a major component that must be taken into consideration when constructing PBNPK models.