large molecules can penetrate. These molecules accumulate and draw in fluid, building pressure in tumor cells that impedes the entry of even small molecules, Dr. Li pointed out (see Figure 7).
The properties of nanomaterials make it difficult to predict how they will penetrate these various biological barriers or be metabolized, which in turn makes it difficult to assess their biodistribution and toxicity, several speakers noted. In most cases, one cannot predict in vivo biodistribution based on nanostructure physical and chemical properties, such as size and charge, Dr. Li noted. He added that nanostructures can distribute to various organs as intact nanoparticles or they can be metabolized or split up into different pieces, which can enter the cells of various organs and reside in them for an unknown amount of time before moving to other organs or being excreted.
“One of the most difficult parts is tracking the multiple components in vivo over time. Some may stay for a long time, some may stay for a short time. You don’t even know whether they stay as one whole piece the whole time. If they stay in the liver, how long are they going to stay, and what problems are they going to cause in the future?” said Dr. Li.
Dr. McNeil added that “a huge issue that we’ve uncovered is stability of the particles. If a nanomaterial is unstable, obviously it will come apart, and in some cases we’ve seen that within a minute of introducing
FIGURE 7 Pharmacokinetics; ADME diagram. ADME stands for absorption, distribution, metabolism, and excretion: the four biological processes that are assessed when a therapeutic or other systemic or topical drug, device, or biologic is evaluated for toxicity.
SOURCE: Li presentation (July 12, 2010).