In vivo Efficacy of PAMAM-Dendrimer-Cisplatin Complexes in SKOV-3 Xenografted Balb/C Nude Mice

Abstract

Loco-regional delivery of cisplatin by Intraperitoneal (IP) administration in ovarian cancer is highly advantageous, since it exposes high concentrations of cisplatin to tumors in the peritoneal cavity. PAMAM-dendrimer-cisplatin complexes are expected to enhance the penetration of tumors in the peritoneal cavity, and aid in enhancing antitumor efficacy of cisplatin. In the present study, PAMAM G4 NH2 and Biotin PAMAM G4 NH2 dendrimer cisplatin complexes were administered intraperitoneally to SKOV xenografted athymic nude mice at a dose of 4 mg/kg. The increase in lifespan of tumor bearing mice and biodistribution of cisplatin in various organs was evaluated after IP administration of cisplatin and dendrimer-cisplatin complexes. The lifespan of mice increased by 41.93% and 25.8%, after treatment with PAMAM G4 NH2 and Biotin PAMAM G4 NH2 dendrimer cisplatin complexes, respectively. A 3-fold increase in the levels of platinum in plasma was observed, after administration of both PAMAM G4 NH2 and Biotin PAMAM G4 NH2 dendrimer cisplatin complexes. Biodistribution studies have shown higher accumulation of platinum in liver, spleen and kidneys with PAMAM G4 NH2 dendrimer-cisplatin complexes. The increased plasma concentration and enhanced tissue accumulation after IP administration of dendrimer-cisplatin complexes offer advantage of administering low dose of cisplatin, which would reduce the dose-dependent toxic effects of cisplatin.