| 摘要 |
<p>A method for encapsulation of antineoplastic agents in liposome is provided, having preferably a high drug:lipid ratio. Liposomes may be made by a process that loads the drug by an active mechanism using a transmembrane ion gradient, preferably a transmembrane pH gradient. The liposome compositions may be prepared by first forming the liposomes in a first aqueous medium, preferably a buffer, then acidifying or alkalinizing the medium thereby establishing a pH gradient, and then admixing the acidified or alkalinized liposomes with the antineoplastic agent. Using this technique, trapping efficiencies approach 100 %, and liposome may be loaded with drug immediately prior to use, eliminating stability problems related to drug retention. Drug:lipid ratios employed are about 3-80 fold higher than for traditional liposome preparations, and the release rate of the drug from the liposomes is reduced. The liposome compositions may be dehydrated and later rehydrated, and may be used in combination with a pharmaceutically acceptable carrier or diluent. An assay method to determine free antineoplastic agents in a liposome preparation is also disclosed.</p> |
