Continuous release of interleukin-2 from liposomal IL-2 (mixture of interleukin-2 and liposomes) after subcutaneous administration to mice.
Recombinant interleukin-2 (IL-2) was strongly and almost completely adsorbed onto small and hydrophobic liposomes by simple mixing 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 displayed better distribution after intravenous administration in mice and improved therapeutic effect against experimental M5076 metastases, as reported previously. In this study, the elimination of IL-2 from the dosing area was investigated when the liposomal IL-2 was administered to mice subcutaneously. The results suggest that the release of IL-2 from this liposome was continuous and almost complete. The mean residence time (MRT) of IL-2 in the dosing area was 11.0 +/- 1.65 hr. This resulted in the 8-fold times enhancement of MRT in the systemic circulation by the presence of liposomes, and IL-2 was detected in the serum for 2 days. Using this liposomal IL-2 is expected to have the potential to decrease the number of injections and enhance the efficacy of IL-2 in immunotherapies and therapies against tumor.
Kanaoka
Eri
E
Drug Metabolism & Pharmacokinetics, Developmental Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, Osaka, Japan. eri.kanaoka@shionogi.co.jp
Takahashi
Kouji
K
Yoshikawa
Takayoshi
T
Jizomoto
Hiroaki
H
Nishihara
Yoshitaka
Y
Hirano
Koichiro
K
D000327:Adsorption; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D051379:Mice
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D007376:Interleukin-2; D008081:Liposomes