Liposome-Enveloped Molecular Nanogels.

Novel hydrogel@liposome particles were prepared by pH-triggered molecular gel formation inside of liposomes loaded with a low-molecular weight gelator derived from l-valine (1). Liposome formation was carried out using l-α-phosphatidylcholine (PC) and cholesterol as components of the lipid bilayer. Molecular hydrogelator 1 and pyranine, a ratiometric fluorescent pH probe, were entrapped in the liposomes at pH 9 and posterior acidification with d-glucono-1,5-lactone to pH 5-6 provoked intraliposomal gel formation. Removal of the lipid bilayer with sodium dodecyl sulfate yielded naked nanogel particles. The systems were characterized by transmission electron microscopy and dynamic light scattering. The hydrogel@liposomes were loaded with doxorubicin, showing a similar release than that observed for liposomes. The hybrid particles described here are the first case of nonpolymeric hydrogel@liposome systems reported. This type of nanocarriers merges the benefits of liposomal vehicles with the inherent stimuli responsiveness and enhanced biocompatibility of hydrogels formed by low-molecular weight molecules, foretelling a potential use in environmentally sensitive drug release.