ABSTRACT
Since this chapter was published in the rst edition of this text,1 a signicant amount of research has been conducted on nanoparticle (NP) disposition that has begun to frame the nature of mathematical models needed to describe NP absorption, distribution, metabolism, elimination (ADME) processes in the body. The author believes that the most fundamental nding in this eld over this period is the intricate association between NPs and biomolecules in vivo, which result in the formation of NP biomolecular coronas that dene the biological identity of NPs in vivo.2-4 The property of NPs that makes them unique, relative to predicting their activity or toxicity relative to small molecules, is that to a large extent their restricted pattern of biodistribution inherent to their particulate structure, dene the nature of their pharmacokinetic properties, and thus therapeutic and adverse effects. Small molecules traverse biological membranes via diffusion or small-molecule transport systems. Particles have different bioenergetics and are transported across cellular membranes
8.1 Introduction ................................................................................................... 135 8.2 What Makes Nanomaterial Absorption, Distribution, Metabolism, and
Excretion Different? .....................................................................................136 8.2.1 Absorption ........................................................................................ 136 8.2.2 Distribution ....................................................................................... 137 8.2.3 Metabolism ....................................................................................... 139 8.2.4 Elimination ....................................................................................... 139
8.3 Pharmacokinetic Models .............................................................................. 140 8.3.1 Physiologically Based Pharmacokinetic Models .............................. 141
8.3.1.1 In Vitro Perfused Tissue Biodistribution Studies ............... 141 8.3.2 Whole-Animal In Vivo Physiologically Based Nanoparticle
Pharmacokinetic Models to Date ...................................................... 143 8.4 Need for Biologically Friendly Characterization Indices ............................. 144 8.5 Conclusion .................................................................................................... 147 References .............................................................................................................. 149
often by vesicular systems. Numerous reviews5-9 have discussed the biodistribution and pharmacodisposition of nanomaterials that make this statement true. This includes, for some specic NPs, detailed analyses of their biodistribution and unique protein interactions. Despite these developments, few actual pharmacokinetic models that quantitate these processes or that take specic interaction mechanisms into consideration have been published. A recent review of NP drug delivery strategies conrms this notion that classic pharmacokinetic parameters have not been determined for most nanomaterials10 except for the more conventional liposomes and polymeric NPs.7
