Biomedical Engineering Reference
In-Depth Information
10.3
Design of Self-Immolative Biodegradable Dendrimers
Polymeric forms of prodrugs have been designed and synthesized for achieving
targetability in malignant tissues, due to overexpression of specifi c molecular
receptive targets [43, 44]. The release of the free drug by a specifi c enzyme is very
crucial for the cleavage of a prodrug-protecting group. Although many dendritic
prodrugs have been designed to target the cancer, only few biodegradable
approaches have been explored till date [16-19, 27, 45]. Toward this end, SIDs have
been lately synthesized, which may open new opportunities for targeted drug
delivery. In contrast to conventional dendrimers, SIDs are fully degradable and
can be excreted easily from the body [29]. Since the dendrimer are multi-immolative,
this effect may increase the number of active drug molecules in targeted tumor
tissues. SID dendritic building units are conceptualized on 2,6-bis-(hydroxymethyl)-
p
- cresol (
7
), which has three functional groups (Scheme 10.2).
DRUG
NH
DRUG
NH
O
O
Enzymatic
cleavage
O
O
O
O
Enzyme
substrate
N
NH
N
N
O
O
O
O
O
O
O
1
2
DRUG
NH
DRUG
NH
NH
DRUG
DRUG
NH
O
O
O
O
S
pontaneou
s
S
pontaneou
s
O
OH
CO
2
O
O
3
4
O
H
2
O
N
N
DRUG
DRUG
NH
2
NH
NH
DRUG
H
2
O
HO
O
O
S
pontaneou
s
O
OH
OH
CO
2
5
6
7
HO
HO
HO
NH
2
DRUG
Scheme 10.2
Mechanism of dimeric prodrug activation by a single enzymatic cleavage [29].
