Liposomes interiorly thickened with thermosensitive nanogels as novel drug delivery systems.

The fundamental structure of liposomes suffers from drawbacks of physical instability. To overcome this problem, the hypothesis of this study was to thicken the liposomal interior by incorporating thermosensitive in situ gel. The so called gelliposomes (GLs) were prepared by a thin-film method using poloxamer solutions as interior aqueous phase. Interior thermosensitive gelation was proved by observation of sustained dissolving of the poloxamer gel after destroying the lipid bilayers with Triton X-100; structural transformation as observed under optical microscopy in a heating-cooling circle also proved the fact of interior gelling. The sol-gel transition temperatures of GLs were in good correlation with those of the bulk poloxamer solution counterparts, which could be easily tailored by adjusting the concentration and ratio of poloxamer 407 (P407) to poloxamer 188 (P188). Membrane anisotropy measurement indicated increased membrane rigidity. In vitro release of the model drug cytosine arabinoside from GLs showed sustained release characteristics for at least one week with typical biphasic kinetics. Study on storage stability and protection against the destroying effect by membrane destroyers indicated improved physical stability in comparison with conventional liposomes. In situ evading of phagocytic uptake by macrophages was observed for GLs, which however should be attributed to the effect of exteriorly adsorbed poloxamers. In conclusion, GLs present distinct characteristics to be used as potential drug delivery systems.