Environmental Engineering Reference
In-Depth Information
nanoparticles. Sometimes, toxicity causes are inherited from techniques used to
produce nanoparticles, e.g. milling. Wet media milling is widely used to produce
nanocrystals. The milling time and rotation speed are key parameters which might
affect traces of metal in samples. This can be controlled by optimizing milling time
and type of ball material [
19
]. Gamma scintigraphy is used for determination of
location of nanoparticles in vivo.
6.5
Industry and Regulatory Approach and Patent
on Toxicity Determination
Nanoparticles have application as fluorescent biological markers detection of pro-
teins, probing of DNA structures, separation and purification of biological mole-
cules and cells, MRI contrast enhancement, tumor destruction via heating, tissue
engineering and drug and gene delivery. FDA nanotechnology products are main in
the area of medical devices, biotechnology, tissue engineering, vaccines, cosmetics,
drug delivery systems, and combination products (drug-device, drug-biologic,
device-biologic or drug-device-biologic that are physically or chemically com-
bined, co-packaged in a kit or separate cross-labeled products). Multi-component
system that may consist of carrier/delivery system (drug or device), therapeutic
agent (drug or biologic), imaging agent, targeting agent, implantable microchip-
based delivery systems that deliver different drugs under controlled conditions and
injectable delivery systems (transdermal microneedles). Imaging agents are mainly
for MRI, ultrasound or for radioactive imagine, while therapeutic agents could be
small molecule, nucleic acid or proteins. Receptor ligands, antibody serves as
targeting moiety. FDA closely keep watch on nanoparticles research advancement
and is working with Center of Drug Evaluation and Research (CDER), Center for
Biologic Evaluation and Research (CBER), National Center for Toxicological
Research (NCTR), and Center for Food Safety and Applied Nutrition (CFSAN).
Currently, approved nanoscale therapeutics include gadolinium chelate for MRI
imaging (Gd-DTPA Dimeglumine), iron oxide particles for MRI imaging
(Feridex), Products using NanoCrystaltechnology (Rapamune, Emend), Liposomes
(Doxil, DaunoXome), Microemulsions (Cyclosporine) and Albumin-bound
nanoparticles (Abraxane), Silver nanoparticles (antibacterial wound dressing),
engineered Calcium Phosphate (NanOssTM, duplicates microstructure, composi-
tion and performance of human bone), nanoparticle dental restorative (3M ESPE
Filtek), Cosmetics (containing lipid nanoparticles or “nanosomes” used as delivery
systems, for controlled release of active ingredients; L
Oreal, Estee Lauder),
sunscreens (containing titanium dioxide and zinc oxide nanoparticles which make
the product appear transparent) (Fig.
6.5
).
As particle size gets smaller, then the particle shows size-specific effects on
biological activity, then it becomes very critical to evaluate to what extent these
small particles get access to tissues and cells at normal conditions. Another question
is how long is the residence time, what is the clearance mechanism, what type of
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