| 摘要 |
Improved liposomal encapsulated cyclosporin formulations are disclosed. The liposomes are efficacious as immunosuppressant agents and in the treatment of drug resistant cancers. The formulations include liposomes comprised of a phosphatidylcholine, cholesterol, a phosphatidylglycerol and a cyclosporin. In one embodiment, the mole ratios of phosphatidylcholine, cholesterol, phosphatidylglycerol and cyclosporin are about 21:0.5:3:1 to 21:1.5:3:1 and 24:0.5:3:1 to 24:1.5:31 wherein the liposomes comprise unilamellar vesicles having a size less than 100 nm. In a preferred embodiment, the compositions are stable upon injection into the blood stream of a mammal, preferably a human. In this embodiment, the preferred ratios of PC:chol:PG:CSA are from about 28:1:3:1 to 40:1:3:1. The preferred formulas are PC:chol:DMPG:CSA wherein the PC is HSPC and the molar ratios are: 28:1:3:1, 30:1:3:1, 32:1:3:1, 34:1:3:1, 35:1:3:1, 36:1:3:1, and 40:1:3:1. Also provided is a liposome encapsulated cyclosporin which provides for a cyclosporin which associates to a significant degree with a liposomal/plasma fraction (vs. cell fraction) of blood as a function of time. Liposomes having these properties are comprised of phosphatidylcholine, cholesterol, dimyristoylphosphatidylglycerol and cyclosporin. These liposomes are unilamellar and have a size less than 75 nanometers and are stable in whole mammal blood. Further provided are liposomes having increased therapeutic indices. The liposomes are stable on storage, contain a therapeutically effective amount of a cyclosporin, provide a liposomal cyclosporin formulation having reduced toxicity, and, in the preferred embodiment, provides a liposomal formulation which is stable in whole blood. |
