Biomedical Engineering Reference
In-Depth Information
d
n
4
y
3
n
g
|
5
Figure 11.8
(A) Chemical structures of backbone-type platinum(IV) prodrugs. (B)
The biodistribution of platinum in various organs and SKOV-3
xenograft tumors after a single i.v. administration of free DSP or
P(DSP-EDA) at a DSP-equivalent dose of 20 mg kg
21
. (Adapted from
Yang et al.
67
with permission from Elsevier.)
(1) the drug's configuration or structure should not be changed and its
therapeutic efficacy should not be impaired; (2) the drug should remain tightly
conjugated in circulation in order to reduce the drug-associated toxicity; and
(3) the drug should be intracellularly released from conjugates efficiently once
inside the tumor cells. The first aspect is the prerequisite of a conjugate, while
the latter two aspects are the elementary 2R (Retention in circulation versus
Release in cells) rules
6
discussed in Chapter 3. Certainly, elementary 2S
(Stealthy in circulation versus Sticky in tumor) rules
6
also should be addressed
as further requirements of a superior prodrug.
Challenges remain even for those proved polymer-drug conjugates,
including safety issues, good manufacturing process, and the cost-effective
scale-up. Most of the proven conjugates use PHPMA or PEG as the
modifier.
69
Although PHPMA and PEG are well tolerated clinically, their
non-biodegradability
is
a
significant
disadvantage,
especially
in
cases
of
chronic parenteral administration and high required doses.
69
Compared to
other
polymeric
nanocarriers,
the
self-assembling
prodrugs
can
be
easily
