During the "Nanotoxicology and Ocular Drug Delivery: One Size Does Not Fit All" session, Nigel Walker (NIEHS-NTP) gave a great overview, highlighting some of the general concerns with nanomaterials. One interesting point he made was that it may not be appropriate to measure the dose of a drug delivered by a nanomaterial by mass as we typically measure dose (mg/kg). Another interesting point that he made is that we’ve known for some time that decreasing the size of a material’s particles increases absorption, which is why some active pharmaceutical ingredients are micronized. This would also apply to the even smaller nanoparticles, so thorough study of absorption is important when using nanoparticles as a drug delivery system. Finally, Dr. Walker mentioned the Nanomaterial Registry, a website sponsored by the NIH that is a tool for the storing, sharing, and analysis of data on nanomaterials and their biological and environmental implications.
Gerard Lutty (Johns Hopkins University) presented some great data comparing several different nanoparticles (magnetic nanoparticles, MNP; chitosan; and PCEP, a novel biodegradable). After injecting the different nanoparticles either intravitreally or subretinally into the eyes of rabbits, they determined that chitosan increased inflammation the most and increased retinal degeneration, while also having a low transfection rate. The different sources of chitosan were analyzed and were later found to contain LPS, which they believe led to the high rate on inflammation in those samples. The PCEP resulted in low inflammatory response, but did have some retinal degeneration and retinal pigment epithelium (RPE) dysfunction. The MNP had the best results, including low inflammatory response and low retinal degeneration with moderate transfection success.
There is still a lot to be learned about the toxicity related to nanomaterials, but there is a lot of very interesting research looking at exactly this topic.