title: Synthesis and biological studies of new lipid-soluble cisplatin analogues entrapped in liposomes.
abstract: A series of highly lipophilic platinum(II) complexes of the type cis-[(RNH2)2PtX2] have been synthesized, where R = ethyl, propyl, isopropyl, butyl, cyclopropyl, cyclopentyl, or neopentyl and X = either long-chain carboxylate, such as decanoate (C10), laurate (C12), myristate (C14), heptadecanoate (C17), stearate (C18), nonadecanoate (C19), or 2,2,3,3-tetramethylcyclopropylcarboxylate, or branched-chain carboxylate, such as neopentanoate, neohexanoate, neoheptanoate, neononanoate, or neodecanoate. These complexes have been characterized by elemental analysis, IR, and 13C and 195Pt NMR spectroscopic techniques. The platinum complexes were entrapped in multilamellar vesicles composed of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylglycerol (DMPG) at a 7:3 molar ratio and tested for antitumor activity. The entrapment efficiency of liposomal platinum (L-Pt) complexes ranged from 60 to 100%. The percentage of T/C obtained after a single i.p. injection of the optimal dose of L-Pt complexes tested against L1210 leukemia ranged from 90 to 125%. These L-Pt preparations did not show significant antitumor activity in mice.
authors.affiliation: Department of Medical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
authors.forename: S
authors.initials: S
authors.lastname: al-Baker
authors.forename: R
authors.initials: R
authors.lastname: Perez-Soler
authors.forename: A R
authors.initials: AR
authors.lastname: Khokhar
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004134:Dimyristoylphosphatidylcholine; D004337:Drug Carriers; D007939:Leukemia L1210 / Q000188:drug therapy; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009368:Neoplasm Transplantation; D010316:Particle Size; D010715:Phosphatidylglycerols
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D010715:Phosphatidylglycerols; C002773:dimyristoylphosphatidylglycerol; D002945:Cisplatin; D004134:Dimyristoylphosphatidylcholine