A low molecular weight gelator forms reproducibly nanogel particles with good temporal and thermal stability and they present accessible hydrophobic domains.

Novel hydrogel@liposome particles were prepared by pHtriggered molecular gel formation inside of liposomes loaded with a lowmolecular 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.

The use of nanocarriers for intracellular transport of actives has been extensively studied in recent years and represents a central area of Nanomedicine. The main novelty of this paper lies on the use of nanogels formed by a low molecular weight gelator (1). Here, nonpolymeric, molecular nanogels are successfully used for intracellular transport of two photodynamic therapy (PDT) agents, Rose Bengal (RB) and Hypericin (HYP).The two photosensitizers (PSs) exhibit different drawbacks for their use in clinical applications. HYP is poorly water-soluble, while the cellular uptake of RB is hindered due to its dianionic character at physiological pH values. Additionally, both PSs tend to aggregate precluding an effective PDT. Despite the different nature of these PSs, nanogels from gelator 1 provide, in both cases, an efficient intracellular transport into human colon adenocarcinoma cells (HT-29) and a notably improved PDT efficiency, as assessed by confocal laser scanning microscopy and flow cytometry. Furthermore, no significant dark toxicity of the nanogels is observed, supporting the biocompatibility of the delivery system. The developed nanogels are highly reproducible due to their non-polymeric nature and their synthesis is easily scaled up. The results here presented confirm thus the potential of molecular nanogels as valuable nanocarriers, capable of entrapping both hydrophobic and hydrophilic actives, for PDT of cancer.