Liposomal vincristine which exhibits increased drug retention and increased circulation longevity cures mice bearing P388 tumors.

Tumors and Increased Circulation Longevity Cures Mice Bearing P388 Liposomal Vincristine Which Exhibits Increased Drug Retention

Drug Toxicity and Increased Activity against Murine L1210 and Liposomal Vincristine Preparations Which Exhibit Decreased

The toxicity and antitumor activity of liposomal vincristine prepara tions have been examined. Vincristine was encapsulated inside egg phosphatidylcholine (EPC)/cholesterol (55/45, mol/mol) and distearoylphosphatidylcholine (DSPC)/cholesterol (55/45, mol/mol) vesicles utilizing transmembrane pH gradient (inside acidic) drug uptake processes. Trap ping efficiencies approaching 100% were achieved...

Effects of quinidine and related compounds on cytotoxicity and cellular accumulation of vincristine and adriamycin in drug-resistant tumor cells.

Quinidine, which has antiarrhythmic activity, greatly enhanced the cytotoxicity of vincristine (VCR) in tumor cells and especially in VCR-resistant sublines of P388 leukemia (P388/VCR) and human myelogenous leukemia. A nontoxic concentration of quinidine increased VCR cytotoxicity in these resistant tumor cells about 50 to 80 times, and the drug in combination with VCR could completely reverse ...

Liposomal and nonliposomal drug pharmacokinetics after administration of liposome-encapsulated vincristine and their contribution to drug tissue distribution properties.

We have determined the pharmacokinetics of liposomal vincristine, in a Lewis lung carcinoma solid tumor model in mice, with the aim of differentiating the contribution of liposomal and nonliposomal (released from liposomes) drug pools to the overall pharmacokinetic profile. Two types of liposomal formulations were used: one composed of 1,2 distearoyl-sn-glycero-3-phosphocholine/cholesterol (Cho...

In vivo circumvention of vincristine resistance in mice with P388 leukemia using a novel compound, AHC-52.

A novel compound partially analogous to nifedipine, AHC-52, was found to sensitize multidrug-resistant tumor cells. AHC-52 at 0.5 microgram/ml completely reversed the in vitro resistance to vincristine (VCR) in VCR-resistant P388 cells (P388/VCR). Of various regimens examined for the in vivo treatment of P388/VCR-bearing mice, the combination of 0.05 mg/kg of VCR with 100 mg/kg twice a day of A...