Biomedical Engineering Reference
In-Depth Information
H
O
O
H
H
H
H
HO
O
H
HO
O
O
HO
H
O
B
H
H
O
H
O
H
H
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OH
H
H
H
H
OH
H
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H
O
O
H
H
HO
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HO
HO
H
H
H
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HO
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B
-
HO
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-
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Complex I
Complex II
H
Figure 6.17
Disintegration of physically cross-linked PVA-borate complex by glucose. (From Manna, U. and Patil, S. 2010.
ACS Appl Mater Interfaces
2: 1521-1527. With permission.)
Chitosan nanoparticles with anticancer drugs physically entrapped usually serve as
tumor-targeting DDSs. Kim et al. [146] prepared a hydrophobically modified glycol chitosan
(HGC) that can form nanosized self-aggregates in an aqueous medium. An insoluble anti-
cancer drug, cisplatin (CDDP), was encapsulated into the hydrophobic cores of HGC nano-
particles by a dialysis method. The drug loading efficiency was up to 80%. Chitosan-based
nanoparticles released the drug in a sustained manner for a week under physiological condi-
tions, controlled by the diffusion mechanism as a result of partitioning between polymer
nanoparticles and surrounding aqueous phase. When the CDDP-HGC nanoparticles were
injected into tumor-bearing mice, they were found to be successfully accumulated by tumor
tissues because of the EPR effect. The selectively localized CDDP-HGC nanoparticles in
tumor tissue showed higher antitumor efficacy and lower toxicity compared to free CDDP.
Polymer-drug conjugates composed of hydrophilic polymers to which drugs are chemi-
cally conjugated via a biodegradable spacer are also used as targeted drug release systems.
By EPR effects, such conjugates can be selectively accumulated at the tumor site, followed
by release of the drug by cleavage of the spacer via hydrolysis or enzymatic degradation.
For example, doxorubicin was conjugated to glycol-chitosan via EDC/NHS coupling
chemistry and a
cis
-aconityl bond was formed between the drug and the chitosan-based
carrier [138,147]. Liberation of doxorubicin was believed to be caused by cleavage of such
cis
-aconityl spacers, which are known to be pH-sensitive with a short hydrolysis half-life
in acidic medium [147]. A noticeable amount of glycol-chitosan self-aggregates was found
to accumulate at the tumor sites due to the EPR effect when they were systemically
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