Pharmaceutical Manufacturing Handbook: Production and

NANOMEDICINE 1279
prises) visibly pursue nanomedicine activities and devote either all or a signifi cant
share of their business to the development of nanomedicines. A characterizing
feature of nanotechnology is its enabling function to add new functionality to existing
products, making them more competitive. For example, Ambisome (Gilead),
a liposomal formulation of the fungicide Fungizone (Bristol - Myers Squibb) that
shows reduced kidney toxicity, had total sales of $ 212 million in 2004. The total
sales of the 38 identifi ed nanomedicine products from all sectors of nanomedicine
are estimated to be $ 6.8 billion in 2004. The market is predicted to further grow
to ∼ $ 12 billion by the year 2012. Currently, nanomedicine is dominated by drug
delivery systems, accounting for more than 75% of the total sales. Twenty - three
nanoscale drug delivery systems are available on the market, but within this group,
three polymer therapeutics alone account for sales of $ 3.2 billion: (i) Neulasta
(pegfi lagrastim; recombinant methionyl human granulocyte colony stimulating
factor and PEG), (ii) Pegasys (PEGylated interferon α 2a), and (iii) PEG - Intron
(PEGylated interferon α 2a), all protein therapeutics to which nanoscale polymer
strings of PEG have been attached to reduce immunogenicity and to prolong
plasma half - life. The most widely used nanotechnology product in the fi eld of in
vitro diagnostics is colloidal gold in lateral fl ow assays, rapid tests for pregnancy,
ovulation, HIV, and other indications. Magnetic nanoparticles are also used for
cell - sorting applications in clinical diagnostics. In the fi eld of biomaterials, the commercial
status of nanotechnology - based dental restoratives is most advanced. Furthermore,
nanohydroxyapatite - based products for the repair of bone defects have
been successfully commercialized. Nanotechnology - based contrast agents are a
market with estimated sales of about $ 12 million. All of the marketed contrast
agents consist of superparamagnetic iron oxide nanoparticles for magnetic resonance
imaging. Nanostructured electrodes are used to improve the electrode tissue
contact, and nanomaterials are used to increase the biocompatibility of implant
housings. Pacemakers with nanostructured (fractal) electrodes are the only active
implants currently on the market that contain a nanotechnology - enabled component
[147] .
In spite of the great success, the safety of nanomedicine is maintained as a
worrying issue. A new discipline appears to exploit the toxicological problem in
nanotechnology applications, called nanotoxicology. Nanotoxicology can be
defi ned as safety evaluation of engineered nanostructures and nanodevices.
Nanomaterials could be deposited in all regions of the respiratory tract after
inhalation. The small size facilitates uptake into cells and transcytosis across
epithelial and endothelial cells into the blood and lymph circulation to reach
potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and
heart. Access to the central nervous system and ganglia via translocation along
axons and dendrites of neurons has also been observed. Nanomaterials could
also penetrate the skin via uptake into lymphatic channels [41] . Although possible
damages of those biodegradable nanomaterials for drug delivery need consideration,
too much fear is needless. Usually they would be ultimately degraded
nearly without any trace. However, hard or nonbiodegradable materials, including
carbon nanotubes, fullerenes, quantum dots, polystyrene, and metal nanoparticles,
should be thoroughly investigated about their toxic effects on our body
before clinical application.