Drug Targeting Organ-Specific Strategies

1.2 Carriers used in Drug Targeting 5
eties as well as drugs are introduced into the carrier molecule. In the case of enhanced permeability
retention in e.g. tumour vasculature [14], the introduction of drugs into the polymer
may suffice.As non-specific adherence to cells is an undesirable property, excessive charge or
hydrophobicity should be avoided in the design of polymeric carriers.
For cancer therapy, the well established N(-2-hydroxypropyl)methacrylamide (HMPA)
polymers have been extensively studied. PK1, a 28-kDa HPMA copolymer containing doxorubicin
(Figure 1.3) is now in clinical testing [15]. Other drugs that have been incorporated
C
H 3
HN
O
CH 3
x
O
CH 3
OH
O
O
OH
OH
HO
NH
O Gly
y
CH 3
CH 3
Gly
Leu
Phe
O
O
OH
OH
doxorubicin
peptidic linker
HPMA copolymer
Figure 1.3. Structure of PK1 (HPMA copolymer doxorubicin), a 28-kDa polymeric carrier–drug
conjugate investigated for its anti-tumour activity in a phase I clinical study. Adapted from reference
[15].
in these polymers are platinates and xanthine oxidase, respectively [16,17]. Furthermore, conjugates
(so called SMANCS) of the anticancer drug neocarzinostatin (NCS) and styrene-comaleic
acid/anhydride (SMA) have been developed for therapy of liver cancer (see Table
1.3). New polymers developed in the last few years include the cationic low molecular mass
chitosan polymers for DNA delivery [18] and highly branched, low dispersity dendrimers
consisting of various chemical origins [19]. Kopeček and colleagues furthermore reported on
the application of Fab’ antibody fragments that can copolymerize with HPMA and drug-containing
monomers to yield a targetable HPMA copolymer–Mce 6 conjugate. In vitro studies
showed that, as a result, the photosensitizer Mce 6 was more efficiently internalized by
OVCAR-3 carcinoma cells than the non-targeted copolymer and hence had greater cytotoxicity
[20].