Abstract
Liposomes recently have been used as a carrier vehicle to enhance antitumor effect against several experimental malignant tumors. In this study, daunorubicin (DNR) was entrapped within positively charged liposomes which were prepared with lecithinstearylamincholesterol at a molar ratio of 7: 2: 1 and the effect of both compounds in free solution and entrapped within liposomes were compared against Lewis lung carcinoma in C57BL/6N mice. Total doses of 12 mg/kg (4 times injections of 3 mg/kg per 2 weeks designated 3 mg/kg x 4/2w, 6 mg/kg x 2/2w, 12 mg/kg x 1 /2w) of free DNR and liposome-entrapped DNR were administered intravenously to mice the 7th day after inoculation with the tumor cells.
The following results were obtained 1) Liposome-entrapped DNR (6 mg/kg x 2/2w, 12 mg/kg x 1 /2w) was more effective than free DNR (6mg/kg x 2/2w, 12 mg/kg x 1 /2w) in inhibiting the tumor growth (p<0.01). 2) Although 6 mg/kg x 2/2w and 12 mg/kg x 1 /2w of free DNR did not prolong the survival time of the mice that of each group (3 mg/kg x 4/2w, 6 mg/kg x 2/2w, 12 mg/kg x 1 /2w) receving liposome-entrapped DNR was prolonged. 3) The effect of saline-liposome itself on the inhibition of the tumor growth and tumor metastases and longevity of the mice was not observed.
Additionally, comparing effects of the liposome-entrapped DNR with free DNR on delayed hypersensitivity examined by footpad reaction of mice, inhibition of delayed type hypersensitivity by free DNR was reduced, when DNR was entrapped within liposomes. However, the inhibition of liposome-entrapped DNR as seen in the delayed type hypersensitivity on humoral antibody production was not observed.
