Formulation kit for liposomal doxorubicin composed of lyophilized liposomes
Stevens, P.J.; Lee, R.J.
Anticancer Research 23(1a): 439-442
2003
ISSN/ISBN: 0250-7005 PMID: 12680245 Document Number: 566489
Background: Doxorubicin can be loaded into preformed liposome by remote loading. Lyophilization of liposomes results in particle size increase and content leakage. Cryoprotectants have been used to improve the stability of liposomal formulations during lyophilization. Here, we have developed a formulation kit for liposomal doxorubicin based on lyophilized liposomes incorporating these cryoprotectants. Materials and Methods: Liposomes composed of egg phosphatidylcholine/cholesterol and containing either glucose or sucrose as a cryoprotectant were prepared by polycarbonate membrane extrusion. These were then loaded with doxorubicin by a pH-gradient-based remote loading procedure either before or after lyophilization and reconstitution. The loading efficiency of DOX was evaluated by gel-filtration chromatography. The effect of lyophilization on the stability of liposomal DOX was also evaluated. Results: Cryoprotectants were effective in maintaining liposome size distribution but not drug retention during lyophilization. DOX loading efficiency of the reconstituted liposomes was near quantitative and comparable to that of freshly prepared liposomes. Conclusion: Liposomal doxorubicin can be produced and stored as a lyophilized kit that can be reconstituted without significant changes to critical formulation properties.