Biomedical Engineering Reference
In-Depth Information
the most important route of delivery at present appears to be systemic distribution
through parenteral delivery, although occupational and environmental exposures
via dermal and inhalation routes are also possible.
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What few studies
are available on QD absorption at the organism level primarily utilize parenteral
intra-venous (iv) delivery.
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QD targeting stud-
ies have shown that QDs with targeting functional groups can be accumulated in
selected target tissues upon intravenous administration. However, distribution to
nontarget tissues in an organism has not been examined and is an area where infor-
mation is critically needed. Due to the high fluorescence of QDs and the metallic
cores, particle deposition within an organism should be readily measurable.
During the past decade, there have been more than 26 FDA approved antican-
cer drugs for clinical use and other therapeutic agents for various conditions from
cardiovascular disease to inflammation.
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Conventional drugs exhibit therapeutic
potential but various limitations hinder clinical translation and disease treatment
success. These limitations include the physicochemical properties of the agents
that prevent them from being efficiently administered in the molecular form.
Majority of the drugs are polycyclic making them insoluble in water. Paclitaxel
and dexamethasone have low water solubility (0.0015 mg/mL and 0.1 mg/mL,
respectively) making them unacceptable for aqueous intravenous injec-
tion.
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A major obstacle that prevents these drugs from reaching their
target is the unspecific distribution with only 1 in 10,000 to 1 in 100,000 mol-
ecules reaching their intended site of action.
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Hence, a much higher concen-
tration or dosage needs to be administered to attain the desired therapeutic effect
with the danger of reaching too close to the toxic level which can therefore, cause
toxicity.
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With these factors in mind, it is desirable to alter
the drug to include features that would pharmacologically guarantee increased
stability, solubility, and specific targeting to the site of action which can be accom-
plished with engineered NMs. Owing to their unique size and properties, NMs
hold promise in improving the therapeutic abilities of various conventional drugs.
The area of medicine in which nanotechnology has contributed the most
in the last 15 years is oncology. Liposomes were the most prominent nano-
carriers in the treatment of cancer being the first commercially available drug
nanocarrier for injectable therapeutics.
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Liposomal doxo-
rubicin was granted with FDA approval for use against Kaposi's sarcoma in
1990 and was later approved for metastatic breast cancer and recurrent ovar-
ian cancer therapy.
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A great variety of nanocarrier based drug delivery
systems with various compositions, physicochemical characteristics, geometry
and surface functionalizations have been generated and are in different stages of
development today.
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Quite a number of nanocarriers for specific drugs are currently undergoing devel-
opment. These nanocarriers reach the disease through either passive or active mech-
anisms.
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The liposomes follow the passive mechanism because they utilize the
enhanced permeability of the neovasculature to localize into the disease site through
enhanced permeation and retention (EPR) mechanism.
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