Drug delivery dominates the use of nanotechnology in pharmaceuticals. Applications include organic nanoplatforms such as polymers,
lipids (e.g., liposomes, nanoemulsions, and solid–lipid nanoparticles), self-assembling structures, and dendrimers as well
as certain inorganic nanoplatforms including metal (e.g., gold and silver), and silica-based nanostructures (1).
Patricia Van Arnum
Setting the framework
The US Food and Drug Administration has not established its own formal definition of nanotechnology, although the agency participated
in a definition of nanotechnology set by the National Nanotechnology Initiative (NNI). The NNI is a federal research and development
(R&D) program established to coordinate the multiagency efforts in nanoscale science, engineering, and technology. FDA and
22 other federal agencies participate. The NNI defines nanotechnology to involve all of the following criteria:
Research and technology development at the atomic, molecular, or macromolecular levels, in the length scale of approximately
1–100 nm range
Creating and using structures, devices, and systems that have novel properties and functions because of their small and/or
Ability to control or manipulate on the atomic scale (1).
Using that definition, nanotechnology relevant to FDA may include R&D that would satisfy the NNI definition and relate to
a product regulated by FDA (2). The specific regulatory requirments, including safety and related issues, are still under
consideration. To gain input on these matters, FDA held a public meeting in September 2008. Earlier this year, FDA launched
a public–private partnership with the Alliance for NanoHealth and eight academic institutions for purposes of expanding knowledge
of how nanoparticles behave and affect biologic systems. The alliance hopes to facilitate the development of tests and processes
that might mitigate the risks associated with nanoengineered products.
ROBERT KOHLHUBER, SOUTHERN STOCK/GETTY IMAGES
Nanodrugs in action
Although the regulatory framework for nanotechnology in pharmaceutical applications and its exact definition are under consideration,
in the context of technology platforms, a broader term of nanodrugs may be used. These nanomedicines are drugs that use platforms based on nanotechnology and related approaches. The technology
evolution of nanodrugs can be seen when evaluating commercial products and clinical and preclinical candidates.
"In the current nanotechnology drug market, the strategy is largely on product-life extension by formulating existing drugs
to enhance their half-lives, improve their oral bioavailability, or efficacy," says Lee Jia, senior project officer of the
Developmental Therapeutics Program for the National Cancer Institute at the National Institutes of Health, who spoke at the
2008 American Association of Pharmaceutical Scientists annual meeting. Advanced nanotechnology systems such as dendrimers
and carbon nanotubes are not yet represented in the list of approved nanodrugs. Unlike the majority of clinical and preclinical
nanodrugs, only 25% of currently marketed nanodrugs are directed toward cancer treatment (3).
There are approximately 28 approved nanodrugs on the market. These drugs primarily use liposomes, polymers, and nanocrystallines
as the basis of formulations. Twelve of these drugs use a liposomal drug-delivery system, 10 a polymeric-based system (such
as pegylation), and 5 nanocrystalline systems. Other systems include albumin-bound platforms (3).
Nanoparticles as vaccine adjuvants.
When examining the nanodrugs in clinical development, more advanced systems are used, and there is a greater emphasis on anticancer
therapeutics (2). Although liposomal and polymeric-based platforms are still represented, more complex systems such as nanocrystals,
nanoemulsions, drugs formulated with gold nanoparticles, and dendrimers are used. Gold nanoparticles, for example, use the
leaky vasculatures of tumors to target delivery of pharmaceutically active compounds to the tumor. Dendrimers, which have
high loading power and specific targeting units, can deliver more active compounds to specific organs and tissues. There are
at least 27 nanodrugs in clinical trials, and approximately 60% of them are for cancer treatment (3).
The value-added focus on nanotechnology in drug development is pushed further in preclinical drug candidates. There are at
least 23 nanodrugs in preclinical development, and 78% of them are anticancer agents. New formulations involve the use of
dendrimers and metallic, ceramic, and virus-based nanoparticles (3).