Stabilization of liposomes with silicone layer improves their elastomechanical properties while not compromising biological features

The liposomes are among the most promising types of drug delivery systems but low stability significantly limits their application. Some approaches proposed to overcome this drawback may affect the liposomes toxicity profile. It is assumed that developed by us and presented here stabilization method involving formation of silicone network within the liposomal bilayer will improve elastomechanical properties of vesicles while not deteriorating their biocompatibility. The silicone-stabilized liposomes were prepared by base-catalyzed polycondensation process of the 1,3,5,7-tetramethylcyclotetrasiloxane (D-4(H)) within the liposomal bilayer. The systematic biological in vitro studies of vesicles obtained were carried out. Moreover, the elastomechanical features investigation employing atomic force microscopy (AFM) measurements was performed. These properties of the liposome membrane are of great importance since they define the nanocarriers' stability as well as play a significant role in their cellular uptake via endocytosis. Applying the Derjaguin-Muller-Toporov (DMT) model, the elastic modulus of the silicone-stabilized liposomes was determined and compared to that characteristic for the pristine liposomes. The in vitro biological evaluation of silicone-stabilized liposomes demonstrated that these vesicles are not toxic for blood cells isolated from healthy donors and they do not induce oxidative stress in HepG2 cells. AFM results confirmed the stabilizing effect of silicone and revealed that the silicone network improves the elastomechanical properties of the resulted liposomes. This is the first report demonstrating that the silicone-stabilized liposomes retain biocompatibility of pristine liposomes' while acquire significantly better elastomechanical features.