Evaluation of Pharmacokinetic, Biodistribution, Pharmacodynamic, and Toxicity Profile of Free Juglone and Its Sterically Stabilized Liposomes

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. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3517-3528, 2011