The present study was aimed to formulate and compare the pharmacokinetic, biodistribution, pharmacodynamic, and toxicity profiles of free
5-hydroxy-1,4-naphthoquinone (
juglone) with sterically stabilized liposomal form. The
liposomes were optimized for size, zeta potential, entrapment efficiency (EE), and in vitro release properties. The optimized formulation had a mean size, zeta potential, and EE value of 137.1 nm, -43.1 mV, and 67.2%, respectively. In vitro release studies showed biphasic pattern with initial burst followed by sustained release over the study period, releasing about 61% after 24 h. In vitro cytotoxicity studies against
melanoma cells indicated that liposomal
juglone was more toxic than free
juglone. Free
juglone had short plasma half-life of about 2 h, whereas liposomal
juglone exhibited significantly improved pharmacokinetics with a 12-fold increase in plasma half-life. Further, biodistribution studies indicated rapid renal elimination of free
juglone, evidenced by its significant localization in kidneys. Conversely, the accumulation of liposomal
juglone in kidneys reduced significantly with enhanced
tumor localization, thereby resulting in enhanced antitumor activity. The histological studies revealed lower levels of nephrotoxicity for liposomal
juglone compared with that of free
juglone. To conclude, sterically stabilized
liposomes could be a promising approach for the intravenous delivery of hydrophobic compounds such as
juglone.