RT Journal Article
SR Electronic
T1 Enhanced antitumor activity in mice after administration of thermosensitive liposome encapsulating cisplatin with hyperthermia.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1203
OP 1207
VO 257
IS 3
A1 K Iga
A1 N Hamaguchi
A1 Y Igari
A1 Y Ogawa
A1 K Gotoh
A1 K Ootsu
A1 H Toguchi
A1 T Shimamoto
YR 1991
UL http://jpet.aspetjournals.org/content/257/3/1203.abstract
AB 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.