Galangin loaded galactosylated pluronic F68 polymeric micelles for liver targeting

Abstract

Galangin possess wide range of pharmacological activities including antiarthritic, hepatoprotective, anti-inflammatory, antibacterial, and anticancer especially in hepatocellular carcinoma. However, its biological use has been limited owing to its poor aqueous solubility, P-gp efflux and rapid in vivo metabolism by cytochrome enzymes. In order to address the drawbacks of galangin, the current work was designed with an objective to prepare liver targeted galangin loaded galactosylated pluronic F68 polymeric (GF68-Gal) micelles. Galactosylated pluronic F68 copolymer was successfully synthesized usi reduction amination method and used for micelle preparation. The prepared micelles were evaluated for micelle size, entrapment efficiency, zeta potential, in vitro galangin release and in vivo biodistribution. The average size of GF68-Gal micelles was found to be around 242±4.6 nm with an entrapment efficiency of about 77.5± 0.34% w/w. In vitro dissolution profile of GF68-Gal micelles revealed controlled release of galangin. Further, biodistribution studies of GF68-Gal micelles showed significant improvement in the amount of galangin in liver at 15 min (around 2.6 folds) and after 30 min (around 7.18 folds) as compared to galangin solution. Such significant increase in galangin amount in the liver for GF68-Gal micelles could be attributed to their efficient targeting to the liver by galactose moieties having affinity towards ASGPR receptor, P-gp and cytochrome enzyme inhibition activity of pluronic F68 reducing the rate of metabolism and in turn elimination. Thus, galactosylated pluronic F68 copolymer can act as a promising carrier system for improving liver targeting of hydrophobic drugs susceptible to P-gp efflux and cytochrome enzyme associated metabolism.

Keywords

• Galactosylated pluronic F68 micelles
• Pluronic
• Galangin
• Controlled drug release
• Biodistribution