Biomedical Engineering Reference
In-Depth Information
FIGURE 5.7
Macrophage uptake of QD-vaccine candidates. Macrophages were labeled with
CD11 that had a green dye. The vaccine candidate was covalently conjugated with a red emitting
QD that was ~12nm in diameter.
Courtesy of Dr George Hui, University of Hawaii at Manoa. (For
color version of this figure, the reader is referred to the online version of this topic)
drug molecules.
27,106
This size range offers the opportunity to increase drug
accumulation and local concentration in target sites by extravasation and, at the
same time, significantly reduce drug distribution and toxicity to normal tissues.
Researchers have also developed other approaches to increase local microvas-
cular permeability and further enhance delivery to solid tumors and other tis-
sues of interest through the use of: (a) physical energy such as hyperthermia
107
and (b) ultrasound.
108
To help maximize drug delivery at targeted locations, a
genetic algorithm-based, area-coverage approach was developed for robot path
planning to a targeted area.
109
This helps avoid obstacles (i.e. blood barriers,
organs, or tissues) through a suboptimal path that will achieve near-optimal
energy consumption for drug delivery. Cellular uptake of particles can occur by
various mechanisms.
5.6.1 Uptake by Phagocytic Cells
The macrophage system is made up of largely phagocytic cells such as mac-
rophages. Generally, particles >1 µm generate a phagocytic response.
110,111
In
a study using immunoglobulin G-opsonized polystyrene beads of defined size
ranging from 0.2 to 3 µm in murine macrophages, Koval
110
reported that phago-
cytosis uptake was size dependent; <30% of 0.2- to 0.75-µm particles compared
to >80% of 2- and 3-µm particles were taken up. On the other hand, Moghimi
reported that entrapment by hepatic and splenic endothelial fenestrations and
subsequent clearance can be avoided by using nanocarriers that do not exceed
200 nm.
10
Other properties such as surface charge and chemistry can also influ-
ence nanocarrier uptake and subsequent clearance by MPS cells.
75,110,111
