Toxicological hazards of inhaled nanoparticles--potential implications for drug delivery

Nanoparticles (NP), here defined as particles with a diameter smaller then 100 nm, are increasingly used in different applications, including drug carrier systems and to pass organ barriers such as the blood-brain barrier. On the other hand, a large body of know-how is available regarding toxicological effects of nanoparticle (NP) after inhalation. More specifically, a number of effects of inhaled NP are attributed to their (i) direct effects on the central nervous system, (ii) their translocation from the lung into the bloodstream, and (iii) their capacity to invoke inflammatory responses in the lung with subsequent systemic effects. This paper gives a brief review on the toxicology of inhaled NP, including general principles and current paradigms to explain the special case of NP in pulmonary toxicology. Since the evidence for health risks of NP after inhalation has been increasing over the last decade, this paper tries to extrapolate these findings and principles observed in inhalation toxicology into recommendations and methods for testing NP for nanocarrier purposes. A large gap is present between research on NP in inhalation toxicology and in nanoscaled drug carrying. This review recommends a closer interaction between both disciplines to gain insight in the role of NP size and properties and their mechanisms of acute and chronic interaction with biological systems.