Controlled release by Ca(2+)-sensitive recombinant human tumor necrosis factor-alpha liposomes.
Recombinant human tumor necrosis factor-alpha (rHuTNF) was entrapped in liposomes consisting of Egg phosphatidylcholine (EggPC) alone, EggPC-egg phosphatidic acid (EggPA) or EggPC-egg phosphatidylglycerol (EggPG). These liposomes, stored in vials, were stable for a month at 4 degrees C. The rHuTNF release from the liposomes were examined in rat plasma and phosphate buffered saline (PBS). rHuTNF was released from the liposomes containing EggPA in rat plasma. The release of rHuTNF was inhibited by EDTA and was induced in PBS containing CaCl2, indicating that this release is induced by Ca2+ ion in the plasma. The release of rHuTNF was promoted by an increase of the EggPA content. In conclusion, we could obtain stable liposomes in a vial and this liposome could immediately release rHuTNF in the rat plasma. Furthermore we were able to control the release rate of rHuTNF from these liposomes.
Yasui
K
K
Department of Formulation Research, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Fujioka
H
H
Nakamura
Y
Y
D000818:Animals; D002118:Calcium / Q000097:blood* / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004355:Drug Stability; D004492:Edetic Acid / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000097:blood / Q000737:chemistry; D010713:Phosphatidylcholines / Q000097:blood / Q000737:chemistry; D051381:Rats; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000378:metabolism*
D003692:Delayed-Action Preparations; D008081:Liposomes; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D014409:Tumor Necrosis Factor-alpha; D004492:Edetic Acid; D002118:Calcium