Effect of composition on the stability of liposomal irinotecan prepared by a pH gradient method

Abstract

Liposomal irinotecan was prepared by pH gradient loading. The parameters that govern this process, including drug loading time, incubation temperature, buffer composition for hydration, and deltapH, were studied. The uptake of irinotecan into liposomal systems in response to the magnitude of the pH gradient was examined. The drug uptake was maximum when the magnitude of deltapH approached 3.7. The effect of the formulation of the liposomes on the stability of the drug delivery system was also studied. Liposomes composed of lipids with a high phase transition temperature, L-alpha-distearoyl-phosphatidyl-choline and hydrogenated soy phosphatidylcholine, were more stable than those composed of lipids with lower phase transition temperatures. Incorporating distearoyl phosphatidylethanolamine-poly (ethylene glycol)2000 into liposomes helped to reduce the size of the liposomes. In addition, the retention of a drug within liposomes was found to be slightly enhanced by including dimyristoylphosphatidylglycerol or dextran sulfate in the liposome formulation.