A significant enhancement of therapeutic effect against hepatic metastases of M5076 in mice by a liposomal interleukin-2 (mixture).
Recombinant interleukin-2 (IL-2) was strongly and almost completely adsorbed onto small hydrophobic liposomes under optimal conditions (liposome: DSPC-DSPG; molar ratio, 10:1; 30-50 nm in size, ratio of IL-2 to liposome: 4.0 JRU/nmol lipid). This liposomal IL-2 improved the distribution of IL-2 after intravenous administration as reported, previously. Liposomal IL-2 (300-10000 JRU/mouse per day) was significantly more effective than free IL-2 alone for inhibiting against the experimental metastases of M5076 in mice. The inhibitory effect of liposomal IL-2 was greatest in the liver. The ED(50) of liposomal IL-2 and that of free IL-2 in the liver were 1640 and 12500 JRU/mouse per day, respectively. This simple preparation (mixture) using IL-2 and liposome suspension is expected to have potential for increasing therapeutic efficacy against hepatic metastases.
Kanaoka
Eri
E
ADME and Toxicology for Screening Developmental Research Laboratories, Shionogi and Co. Ltd., 12-4, Sagisu 5, Fukushima-ku, Osaka 553-0002, Japan. eri.kanaoka@shionogi.co.jp
Takahashi
Kouji
K
Yoshikawa
Takayoshi
T
Jizomoto
Hiroaki
H
Nishihara
Yoshitaka
Y
Uchida
Naomi
N
Maekawa
Ryuji
R
Hirano
Koichiro
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004339:Drug Compounding; D005260:Female; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000556:secondary*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007376:Interleukin-2; D008081:Liposomes; D011994:Recombinant Proteins