Preparation and evaluation of galactosylated vesicular carrier for hepatic targeting of silibinin

Purpose: Silibinin, the main flavonolignan of Silymarin, is used in the treatment of liver diseases of varying origins. Aiming at improving its poor bioavailability of oral products, galactosylated liposomes were introduced in this work for silibinin delivery and targeting to the lectin receptors present on the hepatocytes. Methods: Small unilamellar liposomal vesicles were prepared and p-aminophenyl-β-d-galactopyranoside was covalently coupled. The drug release from liposomes was studied by dialysis method. Plasma, tissue distribution and intrahepatic distribution of free, plain liposomal and galactosylated liposomal encapsulated silibinin were determined following a bolus intravenous injection in albino rats. Various formulations were evaluated regarding silibinin's hepatoprotective activity against CCl4-induced oxidative stress in albino rats. The degree of protection was measured using biochemical parameters like serum glutamic oxalacetate transaminase and serum glutamic pyruvate transaminase. Results: Aggregation of galactosylated liposomes by Ricinus communis revealed the presence of galactose residues on the surface of liposomes. After 24 hours, cumulative drug release percent from galactosylated liposomes was found to be moderate (30.9 ± 1.73). The results of tissue distribution study indicated extensive localization of liposomal formulations in liver cells (galactosylated liposomes, 61.27 ± 3.84 in 1 hour). Separation of the liver cells showed that galactosylated liposomes were preferentially taken up by the hepatocytes (79 of the total hepatic uptake in 1 hour). The introduced galactosylated silibinin produced a significant decrease in both transaminase levels when challenged with CCl4 intraperitonially. Conclusion: A positive outcome of these studies gave an insight that galactosylated liposomes are more effective and suitable for targeted delivery of silibinin to hepatocytes. © 2010 Informa UK, Ltd.