title: Heat-induced drug release rate and maximal targeting index of thermosensitive liposome in tumor-bearing mice.
abstract: To evaluate the rate of drug release at the tumor and maximal drug targeting after administration of thermosensitive liposomes with hyperthermia, a theoretical and experimental method was derived assessing the fraction of drug released from liposomes in a single pass through the heated tumor, F, and the drug targeting index when drug release occurs completely in response to heat (F = 1), DTImax. The F and DTImax were evaluated for four types of liposomes (LUV-1 and LUV-2, thermosensitive large unilamellar liposomes; LUV-3, a nonthermosensitive large unilamellar liposome; and SUV-1, a thermosensitive small unilamellar liposome) using reported data on blood liposome levels and tumor drug levels after the liposomes were administered to tumor bearing mice. DTImax values for LUV-1 and SUV-1 were approximately 6, while the value for LUV-2 with a relatively large systemic clearance was only 2.3. The F values for LUV-1, LUV-2, and SUV-1 with hyperthermia were 0.71, 1.17, and 0.34, respectively, whereas the values for these liposomes without hyperthermia and for LUV-3 with or without hyperthermia were nearly zero. These results confirm earlier findings that LUV-1 and LUV-2 release CDDP almost completely at the heated tumor and that the large DTI value obtained in LUV-1 (DTI = 4.6) was due to its high heat sensitivity and its small systemic clearance.
authors.affiliation: Pharmaceutics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iga
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.forename: H
authors.initials: H
authors.lastname: Toguchi
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood; D004337:Drug Carriers; D008081:Liposomes; D008433:Mathematics; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000188:drug therapy*
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D002945:Cisplatin