Design of functional dendritic polymers for application as drug and ...

Sideratou et al: Dendritic polymers for application as drug and gene delivery systems
M-PEG
(MW 550, 2000)
O
OH + Cl C O NO2O C O NO2 NH2 H2N NH2H2N H N
H
H
N H
NH2 H2N N
O O
N
H N
O
O
O
N
N
H
N
O
H
H
NH2 H2N N
NH2
H
N
N
N
H
N H
NH2 N
O
N
O
O H
O
H N
N
O
H2N
H
O
O
N
H
N
N
N
O
H
H H
O N
N N
N NH2 NH N
2
O
O
O
N O
H
N
O
N
NH2 N O
H
H
H
O
N
N
H
N
H
O
N
N
H
N
H
N
N
O
O
O
H2N N
N H
O
H
O
H
N O
H2N H
N
O
N
N N
N N
N
O NH
N
2
H
H
O
O
N
H
O
H
NH2
N
O
N
O
O
N
H
N
H O
N
N
N H
N
H
N
N
O
H
H
H
H2N N
N
N
O
H
O
H
O
2N
O
O N
O
N
O
NH2 N
H
N N
NH2
H H
N N
H
N O
NH2 H2N O
N
N
H
H
N O
O
N
N
H O
H N
O
N
N
O
O
N
H
O
N H
N
N
H
N
O O
N
H
H
H
O N
NH2 NH2 N
NH2 H2N
H
O O
N
H N
H
N H
NH2 H2N NH2 H2N PAMAM
A
O
M-PEG 4-nitrophenyl carbonate
(A)
NH HN
O
CO
CO
NH
HN
H N
N
H
H
H
NH
HN
N
O O
N
O
CO
O
CO
O
O O
CO CO
NH HN
H N
O
OOCHN
H
N
O N
NHCOO
H N
O O
N
H
N
H
N H
N
O
N
O
O
N
H
N
O
N H
N
O
CO
H
N
NH
N H
NH
N
O H
O
N
O
O
N
H
N
H
H
N
N
N
NH
O
O
N O
H
N
N O
H
H
H
N N
N
O H
N N
O
O
OOCHN
N
O
H
O
H
OOCHN
O
N
N N
N N
N
H
H
O
H
O
N
N
O
H
N
H O
N
N
N
H
O
OOCHN
H
N
O
N
O
OOCHN
O
O
N
N
H
N N
H H
H
O N
N
N
O
O
O
N
H
O O
N
NHCOOHN
N
N
H N
N
H
H
H
O
O N
NH
H
O
H
N
N
H
N
O
N O
N H
H
N
N
O NH
H
O NH
N
O
O
N
N H
N
N
H
H
N
H
O
O N
O
NH
NH
N N
H
H
O N
O
N
NH
N NH
H
N O
O N
N
O
H
O
N H
NH
HN
N
H O O
N
H N
H
N H
NH HN
NH HN
O
O O
CO
CO
CO O
CO O
CO
O
CO O
CO O
CO O
CO O
CO O
CO O
CO O
CO
O CO
O
CO
O
CO
O
CO
O
CO
O
M-PEG-PAMAM
Figure 3. Preparation and structure of M-PEG PAMAM dendrimer of the third generation. Reproduced from Kojima et al, 2000 with
kind permission from the authors and American Chemical Society.
OCH 3
O
O
OH
OH
H3C H2N OH
O
CH2OH OH
O
H 2N
ADR MTX
Figure 4. Chemical structure of the anticancer drugs adriamycin, ADR, and Methotrexate, MTX
NH 2
74
N
N
N
CH 3
O COOH
N
H
COOH
Figure 5. Encapsulation of ADR
by M-PEG(550)-attached (open
symbols) or M-PEG(2000)attached
(closed symbols)
PAMAM G3 (�,�) and G4
(�,▲) dendrimers. The number of
ADR encapsulated per dendrimer
is shown as a function of the
ADR/dendrimer molar ratio during
loading. Reproduced from Kojima
et al, 2000 with kind permission
from American Chemical Society.