Biomedical Engineering Reference
In-Depth Information
O
O
O
MPEO-
b
-PLA-Paclitaxel
CH
3
O
CH
2
CH
2
O
n
CO
m
CH
CH
3
CCH
2
O CH
2
C O
Paxlitaxel
O
O
O
Paclitaxel:
O
NH
O
OH
O
H
OH
HO
O
O
O
O
O
O
O
O
O
PEO-
b
-PLGA-DOX
CH
3
O
PEO
O
C CH
2
O C CHO
CH
2
O
C
C
NH
DOX
m
CH
3
O
PEO-
b
-P(CL-DOX)
CH
2
CH
2
O
CH
2
n
CH
3
O
CH
2
O C CH CH
2
CH
2
CH
2
CH
2
O
m
H
O
C
HN
DOX
OH
O
O
HO
DOX:
OH
OH
O
OH
O
O
CH
3
OH
NH
2
Fig. 6
Example structures of PEO-polyester-anticancer drug conjugates
injected intravenously in rats bearing solid DHD/K12/TRb colorectal tumors on
both legs where the tumor on one side was exposed to ultrasound waves. Application
of low-frequency ultrasound significantly reduced tumor size (Pitt et al.
2004
).
pH sensitive polymeric micelles
- Various polymeric micelles have been designed
that can respond to the acidic pH and show rapid drug release, drug cleavage or micel-
lar dissociation (Torchilin
2006
; Bae et al.
2003b
). The pH of the extracellular space
of most solid tumors is below 7.2, while the pH of normal blood pH is 7.4 (Yatvin
et al.
1984
). The pH of tumor interstitial fluid can further be depressed to values as
low as 6.2 by the administration of either glucose or sodium bicarbonate (Collins
et al.
1989
). After cellular uptake by endocytosis, the micellar carrier may end up in
endosomes/lysosomes that exhibit acidic pHs around 5.0-5.5 (Tang et al.
2003
). The
decreased pH can be used as an internal stimulus triggering preferential drug release
at tumor site for delivery systems that bear pH sensitive groups or linkages.
Two strategies are generally used to provide pH sensitivity in polymeric
micelles. The first strategy involves the selective protonation of acid sensitive
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