Biomedical Engineering Reference
In-Depth Information
Table 3.2 Estimated CD44-Fc coverage by MW HA
HA MW (kDa)
Area (nm
2
) CD44 coverage
(CD44 molecules
available per HA)
6.4 4 49 1 (0.16)
31 10 327 1
132 24 1709 5-6
700 66 13,678 44
1500 105 34,365 110
CD44-Fc is a fusion protein generated by fusing the extracellular
domain of CD44 to the constant region (Fc) of human
immunogloblin G.
Adapted from S. Mizrahy, S.R. Raz, M. Hasgaard, H. Liu,
N. Soffer-Tsur, K. Cohen, R. Dvash, D. Landsman-Milo, M.G. Bremer,
S.M. Moghimi and D. Peer,
Journal of Controlled Release
, 2011,
15
6,
2, 231 [26]
Radius of
gyration (nm)
They also showed that the MMC accumulated in tumours about
30-fold higher than when the drug was administered in the free
form, and four-fold higher than when delivered through unmodified
liposomes. They also found similar results when Dox was used as
the drug. In addition, these high MW HA nanoparticles were also
used to encapsulate the poorly water soluble paclitaxel (PXT). These
particles also showed superior results compared to treatment with
the drug alone [28]. These particles significantly prolonged the blood
circulation time of PXT and increased its accumulation in tumours
with fewer side effects compared to the drug alone. Similar to this,
another group grafted the hydrophobic poly(lactic-
co
-glycolic acid)
(PLGA) chains onto the backbone of hydrophilic HA. The resultant
HA-PLGA self-assembled in aqueous solution to form multicored
micellar particles [30]. These micelles encapsulated Dox during
the self-assembly. These particles, just like other targeted particles
described, exhibited higher cellular uptake and greater cytotoxicity
than the free Dox in cells expressing CD44 but not in cells that do
not express CD44.
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