A
polymer-
drug conjugate was developed by conjugating
doxorubicin (DOX) to [alpha],[beta]-poly[(2-hydroxyethyl)-L-aspartamide] (
PHEA) with a succinic spacer. The suitability of
PHEA-DOX in intraperitoneal
chemotherapy was investigated both in vitro and in vivo. The results showed that the release rate of DOX from
PHEA-DOX in S180
ascites was faster than that in mouse serum or in
buffer solutions. An in-vivo antitumor study revealed that
PHEA-DOX was more effective than DOX against solid S180
tumor after
intraperitoneal injection at the same dose of 10 or 15 mg (DOX eq.)/kg, respectively. At a high dose of 28 mg (DOX eq.)/kg, which was lethal for free DOX to mice,
PHEA-DOX could inhibit 61.5% of solid S180
tumor growth and markedly prolonged the survival time of ascetic S180-bearing mice. The toxicological effects of
PHEA-DOX injected intraperitoneally in normal mice were assessed by using LD50,
body weight increment, electrocardiography, blood biochemical indices, and myocardium histology, giving evidence that
PHEA-DOX displayed considerably reduced systemic and
cardiotoxicity compared with free DOX. All results suggest that
PHEA-DOX has great potential for intraperitoneal
chemotherapy because of its high
therapeutic effects and few adverse side effects.