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

Abstract

Present therapy for human bladder cancer includes the intravesical administration of antiproliferative agents, such as recombinant human interferon alfa (IFN-alpha). 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-alpha hybrid BBDD within liposomes will produce antitumor effects against the human bladder cancer cell line 253J superior to those observed with free IFN-alpha. Adherent cells were cultured in medium alone, in medium containing different concentrations of IFN-alpha, or in medium containing multilamellar liposomes (phosphatidylcholine-phosphatidylserine at a molar ratio of 7:3) that encapsulated saline or IFN-alpha. Cell growth was determined 96-120 hours later. Additional control groups consisted of target cells cultured with free IFN-alpha or with IFN-alpha plus liposomes containing saline. Cytostasis mediated by free IFN-alpha alone or IFN-alpha in the presence of liposome-saline was identical and ranged from 0%-30% (10 IU/mL) to 45%-70% (1,000 IU/mL). Liposomes containing saline produced no effects. Liposome-encapsulated IFN-alpha produced significantly greater growth inhibition than free IFN-alpha: 40%-70% (10 IU/mL) and 80%-90% (1,000 IU/mL), respectively. Moreover, a 253J variant subline selected for resistance to free IFN-alpha was sensitive to IFN-alpha presented in liposomes. These data suggest that the encapsulation of antiproliferative agents such as IFN-alpha in liposomes can improve therapeutic results.

Overcoming Murine Tumor Cell Resistance to Vinblastine by Presentation of the Drug in Multilamellar Liposomes Consisting of Phosphatidylcholine and Phosphatidylserine

“…First, the pharmacodynamic distribution of drugs can be manipulated leading to reduced toxicity (13)(14)(15). Second, as shown here and in other published reports, the encapsulation of chemotherapeutic agents in liposomes can enhance tumor cell sensitivity (7,11,(13)(14)(15) and even overcome the resistance of tumor cells to various chemotherapeutic drugs (7,12) or biological agents (6,8,34,35). ACKNOWLEDGMENT This work was supported in part by funds from grants CA16672 and R35-CA42107 from the National Cancer Institute, National Institutes of Health.…”

Photodynamic therapy of human bladder carcinoma cells in vitro with liposomes as a carrier for protoporphyrindisodiumsalt

“…Numerous reports have been pubushed on the use of liposomes as carrier vehicles for delivery of chemotherapeutic drugs to carcinoma cells (8,9,10). Increasing evidence indicates that cytotoxicity induced by PDT is mediated through the photochemical generation of singlet oxygen via a Type II reaction (Spikes).…”

Review: Application of Nanoparticles in Urothelial Cancer of the Urinary Bladder

“…Oncogene overexpression is one of the major causes of urothelial carcinoma; therefore, the silencing of oncogenes via small interfering RNA (siRNA) coated with liposomes may provide an effective approach to the prevention of bladder cancer [ 98 , 99 ]. Moreover, the intravesical instillation of liposomes encapsulated with cytotoxic agents has been found to improve the efficacy of intravesical therapies used in the treatment of bladder cancer [ 100 , 101 ]. Indeed, one highly feasible treatment modality involves intravesical administration of plasmid-containing liposomes, such as IL-2 [ 102 , 103 ], IL-4 [ 104 ], IL-12 [ 105 ], interferon-gamma [ 106 ], and granulocyte macrophage colony-stimulating factor [ 107 ].…”