Augmentation of Antiproliferative Activity of Interferon Alfa Against Human Bladder Tumor Cell Lines by Encapsulation of Interferon Alfa Within Liposomes

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Abstract
Present therapy for human bladder cancer includes the intravesical administration of antiproliferative agents, such as recombinant human Interferon alfa (IFN-α). The administration of cytotoxic molecules encapsulated in liposomes could provide a more efficient method for such therapy. Therefore, we determined whether encapsulation of the recombinant human IFN-α hybrid BBDD within lipo-somes will produce antitumor effects against the human bladder cancer cell line 253J superior to those observed with free IFN-α. Adherent cells were cultured in medium alone, in medium containing different concentrations of IFN-α, or in medium containing multilamellar liposomes (phosphatidylcholine-phosphatidylserine at a molar ratio of 7:3) that encapsulated saline or IFN-α. Cell growth was determined 96–120 hours later. Additional control groups consisted of target cells cultured with free IFN-α or with IFN-α plus liposomes containing saline. Cytostasis mediated by free IFN-α alone or IFN-α in the presence of liposome-saline was identical and ranged from 0%–30% (10 IU/mL) to 45%–70% (1,000 IU/mL). bposomes containing saline produced no effects. Liposome-encapsulated IFN-α produced significantly greater growth inhibition than free IFN-α: 40%–70% (10 IU/mL) and 80%–90% (1,000 IU/mL), respectively. Moreover, a 253J variant sublime selected for resistance to free IFN-α was sensitive to IEN-α presented in liposomes. These data suggest that the encapsulation of antiproliferative agents such as IEN-α in liposomes can improve therapeutic results. (J Natl Cancer Inst 81:1387–1392, 1989]