Biomedical Engineering Reference
In-Depth Information
HO
O
HO
HO
HO
O
n
O
HO
O
O
HO
O
OH
O
HO
p
HO
HO
OH
HO
m
Dextr an, M
n
17,500
OH
DSPE
DCC
NHS
TEA
DMSO
CHCl
3
81%
HO
O
HO
HO
HO
O
n
O
HO
O
O
O
HO
O
O
OH
HO
O
p
HO
O
-
HO
OH
HO
m
O
O
O
P
HN
O
O
Figure 9.9.
Synthesis of dextran-DSPE at the anomeric end of dextran. DCC:
N,N'
-
Dicyclohexylcarbodiimide. NHS:
N
-Hydroxysuccinimide. TEA: Triethylamine.
A different strategy has been adopted for the delivery of paclitaxel (PTX)
towards xenograft tumours in
in vivo
experiments:
60
SWCNTs, previously
sonicated in the presence of PL-PEG, were subsequently conjugated with
succinic anhydride-modiied PTX, which formed cleavable ester bonds able
to subsequently react with free H
2
N-PEG groups via amide bonds. Results
showed that delivery of PTX from SWCNTs afforded an improved treatment
eficacy over the clinical drug formulation Taxol, as evidenced by its ability
of slowing down tumour growth at a low PTX dose (5 mg/kg). The main
reason for such a higher tumour suppression of SWCNT-PTX conjugates in
comparison with Taxol alone or PEG-PTX is the up to 10-fold higher tumour
uptake of PTX afforded by SWCNT carriers
(Fig. 9.10).
In fact, PEG-PTX
remains a relatively small molecule that tends to be rapidly excreted via the
renal route, thus providing short blood circulation as well as uptake and
treatment eficacy similar to free Taxol. It has been already reported that the
maximum tolerable dose of Taxol for BALB/c mice is between 20 and 50 mg/
kg.
61-63
In this study, the achieved tumour growth suppression by SWCNT-
PTX at 5 mg/kg dose once every 6 days suggests the promising application
of SWCNT drug delivery for effective cancer treatment, also because SWCNTs
have been shown to be safe at least in mouse models.
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