Stability issues are the main drawbacks in the pharmaceutical use of self-assembled lipid vesicles. In this work the stabilizing effect relative to the conversion of the internal structure of liposomes into a soft and elastic hydrogel was investigated. For the design of the gel-in-liposome systems, polyethylene glycol-dimethacrylate (PEG-DMA) was photo-polymerized inside the core of hydrogenated soybean phosphatidylcholine/cholesterol liposomes. The inclusion of a PEG-DMA network within lipidic vesicles affected their intrinsic structural properties improving the mechanical resistance of the assembled nanocarriers against chemical stress. On the other hand, the presence of the polymer did not hampered the possibility to remote load a weak acid model molecule (5(6)-carboxyfluorescein) using a transmembrane pH gradient. Entrapment efficiencies as high as for conventional liposomes were obtained. In addition, the biocompatibility and ability of the novel hybrid vesicle of acting as a valid drug delivery system were not impaired. (C) 2014 Elsevier Ltd. All rights reserved.