Enhanced antitumor activity in mice after administration of thermosensitive liposome encapsulating cisplatin with hyperthermia.
The antitumor effect of cisplatin-(CDDP)-encapsulated thermosensitive large unilamellar liposome (ThLip) administration with hyperthermia (HT) was examined in mice bearing Meth A fibrosarcoma. The tumor Pt levels after ThLip administration were increased in response to HT. The targeting index was approximately 3. The antitumor activity of ThLip + HT, as measured by tumor growth delay or tumor weight inhibition, was larger than that of ThLip without HT or a solution with or without HT. The CDDP dose in ThLip + HT to give equivalent tumor growth delay in solution (40 micrograms/mouse) + HT was about 10 micrograms/mouse, and therefore the targeted drug delivery enhancement ratio was about 4. The ratio correlates with the targeting index. The blood urea nitrogen level, as an indicator of CDDP nephrotoxicity, was increased 7 days after the administration of ThLip (40 micrograms CDDP/mouse) with HT. However, this blood urea nitrogen level rise was independent of the activity enhancement by the liposome. These findings suggest that the HT combined CDDP delivery system using ThLip can decrease the effective CDDP dose, thereby increasing its therapeutic index.
Iga
K
K
Pharmaceutics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Hamaguchi
N
N
Igari
Y
Y
Ogawa
Y
Y
Gotoh
K
K
Ootsu
K
K
Toguchi
H
H
Shimamoto
T
T
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000628:therapy; D006358:Hot Temperature; D006979:Hyperthermia, Induced; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010984:Platinum / Q000493:pharmacokinetics; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D010984:Platinum; D002945:Cisplatin