The Development of Liposomes Containing Interferon Alpha for the Intravesical Therapy of Human Superficial Bladder Cancer

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Abstract
Current therapy of human superficial bladder cancer includes the intravesical administration of antitumor drugs and immunomodulators. The purpose of these studies was to determine whether phospholipid liposomes that bind to human bladder cancer cells can improve the delivery of interferon alpha (IFN-.alpha.) to neoplastic urothelium. The antiproliferative activity of free IFN-.alpha. and IFN-.alpha. encapsulated in liposomes was assessed in vitro against the human transitional cell carcinoma line 253J. The cells were exposed to free and liposome-encapsulated IFN-.alpha. for short periods ranging from 30 minutes to four hours, and inhibition of cell growth was determined three days later. The production of > 25 percent cytostasis of 253J cells by free IFN-.alpha. required four hours of continuous exposure. In contrast, IFN-.alpha. encapsulated in liposomes produced 35 percent and 60 percent cytostasis after a 30-minute and four-hour exposure, respectively. Liposome-encapsulated IFN-.alpha. was also effective (50 percent cytostasis) against a subline of 253J cells selected for resistance against free IFN-.alpha.. Liposomes containing IFN-.alpha. were stable in the presence of human urine. In vivo studies in mice showed that intravesical administration of radiolabeled IFN-.alpha. or radiolabeled liposomes did not yield significant systemic absorption and deposition in distant organs. Collectively, these results suggest that the encapsulation of IFN-.alpha. within multilamellar liposomes may augment its antiproliferative activity, overcome some forms of tumor cell resistance to IFN-.alpha., and proveuseful for intravesical therapy of superficial bladder cancer.