Stealth liposomes for the delivery of trans-resveratrol into solid tumor

Purpose: The aim of the present work was to develop a nanocarrier-based formulation for delivery of trans-resveratrol in solid tumors. Methods: Trans-resveratrol (t-res) was encapsulated into stealth liposomes with different t-res concentration, by a modified hand-shaking method followed by extrusion. All the formulations were characterized in terms of mean diameter, size distribution, t-res loading, t-res stability upon encapsulation and during storage at 4°C. Moreover, in order to assure long term-storage, liposomes encapsulating t-res were freeze-dried in presence of two cryoprotectants (lactose or trehalose) and at two different concentrations (1:5 or 1:10 lipids/cryoprotectant). Finally, we studied the effect of t-res alone or encapsulated into stealth liposomes on human pancreatic tumor cells (BxPC3, MiaPaca and Panc1). Results: All formulations showed a mean diameter between 110 and 135 nm and a polydispersity index (P.I.) lower than 0.2 soon after preparation. Initial t-res concentration did not influence mean diameter and P.I. On the contrary, initial concentration of t-res showed a significative effect on t-res encapsulation efficiency. In particular, higher actual loading (49.9 ???g/ml t-res per mg lipids) was found using higher t-res initial concentration. Lyophilization of liposomes was required, due to the significant t-res release after the first 7 days of storage. Finally, t-res antiproliferative effect, alone or into liposomes, was tested on BxPC3, MiaPaca and Panc1 cells. T-res alone showed an antiproliferative effect in concentration-dependent manner, but this effect was significantly higher when cells were incubate with t-res containing liposomes. Conclusions: In this study, t-res was encapsulated into liposomes stealth at different rates. These formulations showed good technologic characteristic in term of mean diameter and P.I. Moreover, a strong antiproliferative concentration dependent manner effect on BxPC3, MiaPaca and Panc1 cells was observed with t-res and this effect is amplified using t-res containing liposomes stealth. In vivo studies are now ongoing at the University of Sheffield in an experimental model of cancer.