Study On Thermo-Sensitive Liposomes Of BAM

Purpose. The following experiments determined whether intravenous infusions of thermo-sensitive liposome enhance delivery of BAM and prolong survival in mice with metastatic tumors in the brain.Methods. Thermo-sensitive lipsome (ts-lip) and common liposome (cm-lip) were prepared by the film extrusion-PH gradient method. The phase transition temperatures (Tc) of liposome were investigated by differential scanning calorimeter (DSC). To evaluate the effects of brain delivery, pharmacokinetics and biodistribution were investigated and BAM contents in vivo were determined with LC/MS/MS. The mice models of Brain Metastases of Lewis Lung Carcinoma(BMLLC) was established by brain orientation injection of lewis lung carcinoma cells. The model mice were administered B solution or liposome three times i.v. At dose of 10mg/kg followed head hyperthormia at 43°C for 30 min. And histopathologic examination of brain and living fettle were investigated.Results. The number-based average diameters of both cm-lip and ts-lip were in the range of 70-80 nm, and the encapsulated efficiency of both them were above 95%, and the Tc were 42.76°C and 52.93°C for ts-lip and cm-lip, respectively. Hyperthermia promoted the ts-lip to enrich in brain and improved its side effect on heart. Compared with the cm-lip and B solution, the peak drug level was 42.2 ng/g in brain which was higher than the cm-lip(37.6ng/g) and the parenteral solution of B (5.2ng/g). And the peak drug level was 10.45μg/g in the heart which was lower than the cm-lip (12.78μg/g) and B (25.82μg/g). The results stated that the ts-lip had a longer residence time for exposure of the tumor mass to the potential drug.In the brain of mouse administered ts-lip, the tumor cells were mainly concentrated around injection channel and the density of tumor cells was lower/vastly lower than that of tumor cells in the brain of mouse administered cm-lip/B solution. The survival time of mice administered ts-lip(20 days) was remarkably longer than that mice administered cm-lip(15days) or B solution(12 days).Conclusion. Thermo-sensitive liposome of BAM combined with hyperthermia can enhance brain delivery of BAM and prolong survival of mice with metastatic tumors.