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Abstract
Topotecan-entrapping liposomes were prepared by freeze drying double emulsions with hydrogenated soy phosphatidylcholine, N-(carbonyl-methoxypolyethyleneglycol2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and cholesterol. Different inner aqueous phases of different pH values containing topotecan together with different chemicals, such as citrate and sulfate, were used to modify the physicochemical state of the drug to prepare W1/O/W2 double emulsions that were then freeze dried to obtain dry products. Upon rehydration, the dry products, which were stable for at least 6 months, formed into unilamellar liposomes with a high encapsulation efficiency of up to 80% and a mean diameter below 200 nm. The in vitro release experiments demonstrated that different formulations displayed different drug release properties. Thus, stable submicron unilamellar topotecan-entrapping liposomes can be prepared by freeze drying double emulsions, and the drug release can be successfully controlled by altering the physicochemical state of the incorporated drug.