A novel and simple type of liposome carrier for recombinant interleukin-2.
The strong interaction between recombinant interleukin-2 (IL-2) and liposome was characterized and its possible application to drug-delivery control considered. The liposomes were prepared with egg phosphatidylcholine, distearoyl-phosphatidylglycerol (DSPG), dipalmitoyl-phosphatidylcholine, dipalmitoyl-phosphatidylglycerol or distearoyl-phosphatidylcholine (DSPC). Small and hydrophobic liposomes were selected, which were composed of saturated and long-fatty-acid-chain phospholipids. When the composition and the mixture ratio of IL-2 and the liposomewere optimized, morethan 95% ofthe lyophilized IL-2 (Imunace, 350000 JRU) was adsorbed consistently onto the DSPC-DSPG liposome (molar ratio, 10:1; 25 micromol mL(-1); 30 nm in size). Merely mixing IL-2 lyophilized with liposome suspension is convenient pharmaceutically. After intravenous administration to mice, liposomal IL-2 was eliminated half as slowly from the systemic circulation as free IL-2, with more than 13 and 18 times more IL-2 being delivered to the liver and spleen, respectively. After subcutaneous administration of liposomal IL-2 to mice, the mean residence time of IL-2 in the systemic circulation was 8 times that of free IL-2. These results show that IL-2 consistently adsorbs onto the surface of liposomes after optimization of its composition and mixing ratio. Intravenous and subcutaneous administration to mice demonstrates the gradual release of IL-2. Further trials are warranted using these liposomes.
Kanaoka
E
E
Formulation Research & Development Laboratories, Shionogi & Co Ltd. Osaka, Japan. eri.kanaoka@shionogi.co.jp
Takahashi
K
K
Yoshikawa
T
T
Jizomoto
H
H
Nishihara
Y
Y
Hirano
K
K
D000465:Algorithms; D000818:Animals; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010316:Particle Size; D010743:Phospholipids; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D010743:Phospholipids; D011994:Recombinant Proteins