In particular, the levels of EGFR protein expressed by the human

In particular, the levels of EGFR protein expressed by the human hepatocellular carcinoma cell line HA22TVGH were evaluated by Western blot analysis. As shown in Figure 3A, the cell line intensely expressed the receptor. Based on this result, HA22TVGH cells were used for testing the inhibitory effects of tyrphostin AG 1478 free and loaded into the NLC on cell growth. In this regard, Wortmannin DNA-PK the clonogenic assay is currently considered the gold standard assay for the assessment of the ability of drugs in killing tumor cells in vitro experi ments. In fact, this assay is a reliable method to meas ure the reproductive survival of tumor cells capable of clonal expansion. In this regard, to evaluate the effect of tyrphostin AG 1478 free and loaded into NLC on the ability to form colonies, HA22TVGH cells were subjected to clono genic assay.

As shown in Figure 3B, the ability of HA22T VGH cells to form colonies was slightly inhibited Inhibitors,Modulators,Libraries after treatment with free tyrphostin AG 1478 up to a con centration of 25 uM, whereas, the delivery of tyrphostin AG Inhibitors,Modulators,Libraries 1478 from the NLC inhibited Inhibitors,Modulators,Libraries colonies formation to approximately 90% at 25 uM, therefore potentiating the activity of tyrphostin AG 1478 to inhibit HCC cell growth. The results show that tyrphostin AG 1478 loaded NLC maintain antitumor activity, demonstrating that the entrapment of tyrphostin AG 1478 into NLC does not cause an activity reduction of the drug, but even reduces cell colony survival much more than free drug.

Therefore, the results demonstrate an improved thera peutic efficacy of tyrphostin AG 1478 loaded NLC com pared to the free drug and suggest that Inhibitors,Modulators,Libraries lipid nanoparticles could have a great potential as tyrphostin AG 1478 tar geted delivery systems. Finally, considering that solid tumors present much more favorable conditions for preferential accumulation of colloidal sized drug delivery systems such as NLC, these systems can Inhibitors,Modulators,Libraries be useful for application in cancer therapy. Conclusion In this paper, the realization of NLC with suitable char acteristics for parenteral delivery of tyrphostin AG 1478 in the treatment of cancer was described. In particular, by using the precipitation technique, different lipid com positions were used to obtain the best NLC system in terms of drug loading, mean particle size, and zeta po tential values.

The amount of tyrphostin AG 1478 en trapped into NLC resulted to be higher into those systems obtained by using a mixture of solid and liquid lipids compared to those obtained by using only the solid lipid. Moreover, the un pegylated nanoparticles released the tyrphostin AG 1478 slower than the pegy lated systems and the amount of unreleased drug was still inside of each nanoparticulate sample. This result sup ports the great potential of these nanostructures as drug delivery systems with a dispersing and protecting action on drugs, in aqueous media.

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