All together these results in terms of LC, mean size and zeta potential values indicated that the best NLC all targets to be proposed as drug delivery systems for tyrphostin AG 1478 seem to be those obtained by using the mixture be tween tripalmitin and the Inhibitors,Modulators,Libraries liquid lipid, that is NLC D and NLC C. For this reason, these latter systems were chosen to perform successive charac terization in terms of drug release studies and in vitro biological assay. In particular, release studies were carried out in different incubating media such as phosphate buf fer solution at pH 7. 4ethanol mixture or human plasma. The use of this modified dissol ution medium to test preparation containing poorly aqueous soluble active substances was in accordance to the European Pharmacopoea.

In Figures 1 and 2, the released Inhibitors,Modulators,Libraries drug, expressed as weight percent ratio between released drug and the total entrapped drug, is reported as a function of incubation time respectively in PBSethanol and in human Inhibitors,Modulators,Libraries plasma. The release trend could be explained considering the high hydrophobic behaviour of the drug that shows a higher affinity for the system obtained by using the un pegylated liquid lipid mixed with tripalmitin as for lipid matrix composition than for that obtained by using the Inhibitors,Modulators,Libraries pegylated lipid. On the other hand, the lower affinity for the pegylated lipid could give a preferential drug depos ition in the outsides shell of the NLC during the prepar ation process, and consequently a burst effect in the release profile of the drug could be evidenced.

Therefore, a modified release of tyrphostin AG 1478 from the un pegylated systems can be seen in the graphic, being the amount of released tyrphostin AG 1478 about the 90 wt% of the total entrapped amount after 72 hrs incubation. It was also evaluated that the amount of un released Inhibitors,Modulators,Libraries tyrphostin AG 1478 was still inside NLC sample in the intact form at every incubation time. This result supports the great potential of these nano structures as drug delivery systems for systemic adminis tration of drugs with low solubility andor instability in aqueous media. The release profile of tyrphostin AG 1478 was also in vestigated in human plasma, and obtained data are re ported in Figure 2. Compared to the drug release profiles obtained in PBS at pH 7. 4, a faster drug release is evidenced from either the pegylated or the un pegylated systems in human plasma, probably due to the different composition of the medium, such as the presence of proteins and enzymes in the medium. However, also in this case, the un pegylated system released the drug slower than the pegy lated one. This fact also in this case could be explained considering a higher affinity of the drug for the system Sunitinib cost obtained by using the un pegylated liquid lipid mixed with tripalmitin.