Pharmacokinetics and physiologically-based pharmacokinetic modeling of nanoparticles

The worldwide commerce involving nanoparticles will soon reach $1 trillion and already we have more than 600 commercial products containing nanoparticles. Because nanoparticles are invisible and little is known about their toxicities, there has been concern about health effects in humans. As toxicology is a continuum of pharmacokinetics and pharmacodynamics, this is a review of recent advances on pharmacokinetics and physiologically-based pharmacokinetic (PBPK) modeling involving nanoparticles. We provide a synopsis of the state-of-the-science on the absorption, distribution, metabolism, and excretion (ADME) of nanoparticles in mammals, as well as some of the unique applications of pharmacokinetics to nanotechnology. Earlier, the main emphasis of pharmacokinetics of nanoparticles centered around the "control release" of drugs. Thus, drugs encapsulated by lipidic nanoparticles or bound to nano-particles form a controlled-release mechanism. The end results included, among others, enhancement of therapeutic duration and reversion of multidrug resistance. As the science advances in this area, the resulting achievements included: (1) utilizing nanoparticles as delivery vehicle for drugs, drug combinations, or genetic materials; (2) capitalizing on physico-chemical properties and tissue affinity of nanoparticles for medical imaging; (3) potentiating drug effects on immunotoxin and anticancer drugs; and (4) creating "stealth" capability from body's defense system. More recently, the application of biologically-based computer modeling to nanoparticles made it possible not only for inter-species, inter-routes, and inter-dose extrapolations but also for the integration of the modern tumor biology and computational technology for the possible improvement of cancer chemotherapy. Although pharmacokinetics and PBPK modeling of nanoparticles are still in their infancy, impressive innovations have already been demonstrated in their applications to medical sciences. Nanotoxicology is one of the most promising and fertile areas of science given the importance of nanoparticles to the economy of the 21st century, their possible environmental fates, as well as the potential health concerns of these particles.