title: Dendrimer-platinate: a novel approach to cancer chemotherapy.
abstract: A polyamidoamine (PAMAM) dendrimer generation 3.5 with a sodium carboxylate surface was conjugated to cisplatin giving a dendrimer-platinate (dendrimer-Pt; 20-25 wt% platinum) which was highly water soluble and released platinum slowly in vitro. In vivo the dendrimer-Pt and cisplatin were equi-active i.p. against i.p. L1210, and at high dose dendrimer-Pt given i.p. showed activity against i.p. B16F10 whereas cisplatin did not. Additionally, when administered i.v. to treat a palpable s.c. B16F10 melanoma, the dendrimer-Pt displayed antitumor activity whereas cisplatin was inactive. Measurement of platinum levels in blood and tissues after i.v. injection of cisplatin (1 mg/kg) or dendrimer-Pt (15 mg/kg)-the maximum tolerated dose (MTD) of these compounds-showed selective accumulation of the dendrimer-Pt in solid tumor tissue by the EPR effect (a 50-fold increase in area under curve compared with cisplatin). The dendrimer-Pt was also less toxic (3- to 15-fold) than cisplatin and thus has potential for further investigation as a novel antitumor approach.
authors.affiliation: Centre for Polymer Therapeutics, The School of Pharmacy, University of London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Malik
authors.forename: E G
authors.initials: EG
authors.lastname: Evagorou
authors.forename: R
authors.initials: R
authors.lastname: Duncan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D050091:Dendrimers; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D011073:Polyamines / Q000737:chemistry*; D012995:Solubility; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D002945:Cisplatin