Biomedical Engineering Reference
In-Depth Information
small unilamellar vesicles (suVs, 80 nm, sm/Chol = 2:1) administered at the dose of
6 mg lipid/kg body weight show high liver uptake (about 60% of injected dose 23 h
postinjection), while at doses exceeding 120 mg/kg, liver uptake is much lower and
reaches plateau at 20% of injected dose [79].
The surface charge and the charge density of nanocarriers can be controlled
by introducing certain components in the lipid bilayers. in general, the presence of
a high electrostatic surface charge promotes the interaction of nanovesicles with
biomolecules (e.g., serum proteins) and cells. it has been shown that neutral and
positively charged nanocarriers acquire a negative charge in the circulation, prob-
ably due to the adsorption of plasma components (e.g., α2-macroglobulin) [80].
However, regardless of charge acquired on contact with plasma, the tissue uptake of
negatively charged nanocarriers after intravenous (iV) injection is more rapid than
of neutral or positively charged vesicles as indicated by their faster clearance from
the circulation [1, 59].
3.3.2
Background clearance
To clearly visualize the tumor, it has to accumulate a sufficient amount of radioac-
tivity above the background level of activity demonstrated by normal tissues.
generally, a target-to-background ratio of at least 1.5-2 is necessary for detecting a
pathological site and providing diagnostically significant image [81]. As the radio-
activity of agents remaining in the blood form the main source for the background,
proper identification and selection of the radiopharmaceutical plasma half-life is
essential. Long circulation is important for higher tumor accumulation via the
enhanced permeability and retention (Epr) effect [82, 83]. At the same time, the
remaining blood activity decreases the target-to-background ratio. on the other
hand, too short plasma half-life of a contrast agent results in great reduction in
tumor accumulation, although providing low background activity. Thus, a half-life
of about 6-12 h appears to be ideal to allow for sufficient accumulation of nanocar-
riers in inflamed or cancerous targets yet provides enough background clearance to
permit early identification of the target [20, 84, 85].
3.3.3
active Background removal
The target-to-background ratio can also be increased by developing special protocols
for decreasing the background signal. Thus, the method was described for the rapid
removal of nanocarriers from the circulation prior to the imaging [86]. in this method,
biotin-coated nanocarriers are injected intravenously and allowed to accumulate in
the tumor. Then, after 4 h, avidin is injected to induce the aggregation of the biotin-
coated nanocarriers due to strong avidin-biotin interaction. This resulted in rapid
removal of aggregated nanocarriers from the circulation by liver and spleen. using
this technique, the tumor-to-blood ratio increased to 13.8 compared to about 0.9 in
the control. This method has great potential for rapid imaging using nanolipidic
vesicles.
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