Similarly, Cell Therapeutics (Seattle, WA, http://www.cticseattle.com/) is developing a nanotherapy for lung cancer ("Xyotax") that binds Taxol to a poly-glutamate polymer to deliver the drug to tumor cells more efficiently. This nanoformulation remains in the tumor longer than other formulations and has fewer toxic side effects.

In addition to cancer agents, biomedical nanoscience is focusing on improving methods for delivering various drugs and biologics to specific cellular targets. This approach may be particularly important in gene-therapy development, which has been stymied by difficulties in finding suitable transport agents to carry nucleic acid to the diseased target cell. New nanoscale structures designed to bind and neutralize anthrax toxins may protect people from this and some infectious diseases.

Researchers at Montana State University (Bozeman, MT, http://www.montana.edu/) are using disarmed viruses and protein-cage technology to deliver therapeutic and imaging agents to specific tissues and cells. The scientists believe that such containers have multiple applications for carrying and delivering antibodies, peptides, and other therapies and have licensed this technology to SpeciGen (Palo Alto, CA, http://www.specigen.com/) to develop protein-cage drug delivery products.

In response to these developments, FDA is expanding its expertise to assess such products better as they move from laboratories to commercial development. One issue is the need for added scrutiny of safety concerns related to nanotherapies, starting with the numerous sunscreen products incorporating nanoformulations that are clear and more readily absorbed. The Center for Technology Assessment (CTA) considers these products dangerous and filed a petition with FDA in May calling for the agency to pull all over-the-counter nanotechnololgy-based sunscreens off the market until manufacturers can prove they are safe and present no hazard to public health.

Sunscreens raise alarms

FDA weighs concerns

Many of the issues raised in the CTA petition have been under scrutiny at FDA for many years. Nanoparticles have been used in the research and development process for drugs and biologics to enhance biological markers, probe DNA structures, purify biological molecules, enhance MRI agents, and develop drug delivery mechanisms, explains Nakissa Sadrieh, associate director for research policy in the Office of Pharmaceutical Science of the Center for Drug Evaluation and Research (CDER).

FDA has not detected any safety concerns related to particle size in drug products, however, and believes that the existing battery of preclinical safety tests, which require the administration of several high doses to multiple animal species for a long period of time, would uncover relevant safety problems. FDA has regarded nanomaterials as substantially the same as larger counterparts, Sadrieh points out, and has not required special testing of nanomaterials.

At the same time, FDA recognizes that nanoparticles in drugs and cosmetics may gain access to tissues and cells more easily and that little information is available about how long nanoparticles remain in the body, how they are eliminated from tissues and blood, and whether they have additional effects on cellular functions or on different cell types. FDA would like more research about whether the inhalation of nanoparticles raises specific safety issues, whether local sensitization arises from subcutaneous injection of nanoproducts, and whether dermal applications could spread to local lymph nodes. The agency advises manufacturers to assess any differences in the absorption, distribution, metabolism, and excretion profile of nanoparticles compared with larger particles of the same drug, including whether they have accurate methods for measuring drug levels in the blood and their eventual elimination from the body.