Concepts and Strategies for the Site Specific Delivery of Nanocarrier Based Delivery Systems for Treating Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is most common lethal malignancy worldwide. About 80% of liver cancer cases are attributed to the combined effects of Hepatitis B and C virus infections. The factors affecting development of HCC include cirrhosis and histological markers of increased liver cell proliferation, environmental, dietary and lifestyle of the person. Treatment options depend on the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic deterioration. The primary option for some of the patients include hepatic resectioning, locoregional ablation, liver transplantation, ultrasound-guided tumor injection with absolute ethanol or tumor thermoablation with radiofrequency. Most common drugs like sorafenib, doxorubicin and daunorubicin have been used widely for treatment of HCC. A number of novel formulations like polymeric nanoparticles, nanocapsules, liposomes, nanoemulsions, microsphere, hydrogels, dendrimers, polymeric micelles has been reported for the treatment of HCC. The advantages of novel drug delivery systems (NDDS) is based on the ability to modify the bio-distribution, pharmacokinetics and pharmacological activity, prolonged efficacy and duration of drug activity, improved patient compliance, drug targeting to the site of action, enhancement of solubility, bioavailability, protection from toxicity, enhancement of stability. The carriers for liver specific drug delivery include liver-specific asialoglycoprotein receptor on mammalian hepatocytes. The natural ligand i.e. asialofeutin, or synthetic ligands with galactosylated or lactosylated polymers have been developed for significant targeting to the liver.