Nanoparticles to Cross Biological Barriers - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 86

such as pulmonary, nasal, oral, and transdermal are discussed along with
systemic biodistribution and interactions of nanoparticles with their bio-
logical environment. A discussion of design considerations to optimize the
delivery system is included to provide a guide for the engineering of a deliv-
ery system for specific applications.
Introduction
Nanotechnology [1] has a very broad definition depending on scale, and nano-
medicine is a multidisciplinary field using nanotechnology for medical applica-
tions such as therapy and diagnosis [2-8]. While the National Nanotechnology
Initiative (NNI) defines nanotechnology as materials that have an upper size
limit of 100 nm (www.nanogov.com), many nanocarriers ranging from 5 to
150 nm are now in various phases of clinical trials [7-9]. Nanomedicine can
provide an opportunity for improved drug development because early clini-
cal phases often cast light on the side effects limiting the drug's therapeutic
dose. In addition, a sharp increase over the past few years in the number of
patent applications and high-impact factor publications in this area highlight
the level of interest in nanomedicine by both academic and industry investi-
gators [10]. In 2009, the NNI budget of $1.5 billion was allocated to a number
of funding agencies, reflecting a steady growth in addition to the $8 billion
invested since 2001. To develop a common direction in the fight against cancer,
the National Cancer Institute (NCI) showed a clear commitment to nanomedi-
cine with the recent allocation of $144 million. This initiative was established
with clear objectives to form academic and commercial partnerships, establish
outstanding training programs, leverage additional funds, and reduce the risk
of investment in new products (www.nano.cancer.gov).
Current therapies and diagnostic systems are still lacking in precision, effi-
cacy, sensitivity, and safety. A large percentage of drug candidates (50-80%)
developed by the pharmaceutical industry fail during clinical trials. In addi-
tion, the efficacy of many drugs that are being approved for therapy are still
limited for certain diseases, leaving ample room for improvements using
new technologies. Generally, therapeutic drugs have to be administered in
high-dose regimens because of short half-life, thereby increasing the sys-
temic toxic side effects. The physico-chemical properties of drugs, such as
solubility, charge, molecular size, and stability, affect their systemic phar-
macokinetics. In general, nanocarriers deliver drugs in the optimum dosage,
increase drug's bioavailability, enhance drug's efficacy, improve patient com-
pliance, and allow the use of drugs with a broad range of physico-chemical
properties. Nanotechnologies could thus provide new approaches for deliv-
ering drugs (small molecules, proteins, nucleic acids) at the optimal dose
in a controlled release to specific tissues, cells, and even cellular organelles.