Antitumor efficacy and biodistribution of liposomal sepantronium bromide (YM155), a novel small-molecule survivin suppressant

• Liposomal YM155 greatly improved the level of YM155 circulating in the blood.
• Liposomal YM155 showed unexpectedly high accumulation in the kidneys.
• High tumor accumulation of liposomal YM155 was observed based on the EPR effect.
• Strong antitumor effect by weekly bolus injection of liposomal YM155 was observed.

Sepantronium bromide (YM155) exhibits time-dependent antitumor activity, although the plasma half-life of YM155 after a bolus intravenous (i.v.) administration is very short. Therefore, greater antitumor efficacy is obtained by continuous infusion than by bolus i.v. administration. In the present study, we attempted to liposomalize YM155 to obtain a longer circulation time than that achieved by bolus i.v. administration and yet retain sufficient antitumor activity. Encapsulation of YM155 in polyethylene glycol-coated liposomes extended the half-life of the drug, and high tumor accumulation of the drug was observed. Bolus i.v. administration of liposomal YM155 by a weekly administration regimen showed antitumor activity comparable to that obtained by the continuous infusion without severe toxicity in a murine xenograft model. Therefore, this liposomal formulation can be a new dosage form of YM155 that achieves sufficient efficacy and safety and is a more convenient administration regimen for users. It should be noted that liposomal YM155 showed unexpectedly high accumulation in the kidneys. This is a specific finding for liposomal YM155, offering important information for the consideration of the potential toxicity of liposomal YM155.

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