Median duration of progression free and overall survival was calculated using the Kaplan Meier method. p values according to the log rank test. Background Hepatocellular carcinoma represents the fifth most common cancer sellectchem worldwide and third leading cause of cancer related mortality globally, maintaining a dismal prognosis since intermediate and advanced stages still account for a large percentage of cases. Therapeutic op tions in advanced stage have been quite limited so far, until the discovery of new therapeutic agents that target the mo lecular pathways involved in hepatocarcinogenesis. Epidermal growth factor receptor is expressed at high levels in a variety of solid tumors. In HCC, the overexpression of this receptor has Inhibitors,Modulators,Libraries been associated with late stage disease, increased cell proliferation, and degree of tumor differentiation.

In addition, activation of EGFR pathway is a prognostic predictor of survival in patients with HCC. Therefore, EGFR represents a good potential molecular target for biologic therapy of HCC. Tyrphostins are protein tyrosine kinase inhibitors. Among them, the tyrphostin AG 1478, Inhibitors,Modulators,Libraries 4 6,7 dimethoxyquinazoline, a competitive inhibitor Inhibitors,Modulators,Libraries of the ATP binding site in the kinase domain of EGFR, inhibits proliferation and induces death of liver tumor cells through EGF receptor dependent and independent mechanisms. Previous studies also revealed that tyr phostin AG 1478 has no cytotoxic effects per se against normal hepatocytes, while it prevents proliferation and in duces apoptosis in human HCC cells. Moreover, it en hances the sensitivity to cytotoxic drugs like cisplatin and doxorubicin.

Therefore, tyrphostin AG 1478 could be a potential therapeutic drug for the treatment of HCC. How ever, it has not been proposed as a potential antineoplastic drug in HCC yet. Recently we have successfully realized novel lipid based drug delivery systems for several lipophilic anti cancer compounds by selecting the proper lipid Inhibitors,Modulators,Libraries mixture to obtain nanostructured lipid carriers and by using the nanoprecipitation method. By in vitro studies, we have also demonstrated the increased antitu mor efficacy of the drug when loaded into NLC com pared with free drug. Thus, in the present study, we describe the prepar ation of novel tyrphostin AG 1478 loaded NLC by selecting the suitable matrix composition in order to achieve the chemical physical characteristics Inhibitors,Modulators,Libraries and release profile suitable for parenteral administration of this drug. Moreover, on the best formulation, in vitro cell viability assays were carried out to compare the anti proliferative currently activity of the drug entrapped into NLC versus free drug on HA22TVGH cells.