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Asulacrine (ASL) is an inhibitor of topoisomerase II, which has shown potential against breast and lung cancer. It is a poorly water soluble drug. To allow intravenous (i.v.) administration, ASL was formulated as a nanocrystalline suspension by high pressure homogenization. The nanosuspension was lyophilized to obtain the dry ASL nanoparticles (average size, 133 ± 20 nm), which enhanced both the physical and chemical stability of the ASL nanoparticles. ASL dissolution and saturation solubility were enhanced by the nanosuspension. Differential scanning calorimetry and X-ray diffraction analysis showed that the crystallinity of the ASL was preserved during the high pressure homogenization process. The pharmacokinetics and tissue distribution of ASL administered either as a nanosuspension or as a solution were compared after i.v. administration to mice. In plasma, ASL nanosuspension exhibited a significantly (P < 0.01) reduced Cmax (12.2 ± 1.3 μg ml−1vs 18.3 ± 1.0 μg ml−1) and AUC0–∞ (18.7 ± 0.5 μg ml−1 h vs 46.4 ± 2.6 μg ml−1 h), and a significantly (P < 0.01) greater volume of distribution (15.5 ± 0.6 l kg−1vs 2.5 ± 0.1 l kg−1), clearance (1.6 ± 0.04 l h−1 kg−1vs 0.6 ± 0.04 l h−1 kg−1) and elimination half-life (6.1 ± 0.1 h vs 2.7 ± 0.2 h) compared to the ASL solution. In contrast, the ASL nanosuspension resulted in a significantly greater AUC0–∞ in liver, lung and kidney (all P < 0.01), but not in heart.