Biomedical Engineering Reference
In-Depth Information
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Figure 11.1
Sketch of a typical polymer prodrug.
various properties and functionalities. In this chapter, we focus on the low
molecular weight drugs chemically modified with polymers for cancer drug
delivery, some of which are generally called polymer-drug conjugates.
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The ultimate goal of cancer drug delivery is to increase the tumor selectivity
or targeting ability to enhance the therapeutic efficacy and reduce side effects.
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According to the three stages of the cancer drug-delivery process discussed in
Chapter 3, such an ideal anticancer prodrug should be able to sustainably
circulate in the blood compartments, efficiently extravasate into the tumor and
penetrate through the tumor tissue, and finally get into tumor cells and release
the parent drug.
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Most polymer-based prodrugs endow the parent drugs with
adequate aqueous solubility and improved tumor targeting. However, current
polymer prodrugs have some inherent drawbacks, e.g. low drug content and
low tumor specificity, that limit their further translation from the benchtop to
the bedside. Thus, design of novel prodrugs with desirable properties is needed.
In this chapter, we briefly review the methods for preparing conventional
polymer prodrugs and their associated problems, and summarize new
strategies showing great promise and the remaining challenges in translational
prodrugs.
11.2 Design of Polymer-Based Prodrugs
As shown in Figure 11.1, a polymer-based prodrug consists of three parts: the
drug, the linker, and the modifier. The drug determines the potency, while the
linker and modifier determine where the drug goes to exert the potency
(targeting). Anticancer drugs good for making prodrugs must have at least one
reactive site to be anchored to the polymer modifier via a linker. The parent
drugs must have high potency to avoid using too much excipient(s). The most
investigated
anticancer
drugs
are
doxorubicin
(DOX),
paclitaxel
(PTX),
camptothecin (CPT), and its derivatives (e.g. SN38).
11.2.1 Linkers
Common chemical linkers for the synthesis of prodrugs for cancer therapy,
such as ester, amide, hydrazone, and disulfide bonds, have already been
summarized by Mahato et al.
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An ideal linker rendering the prodrug maximal
