Gelation of the internal core of liposomes as a strategy for stabilization and modified drug delivery I. Physico-chemistry study

[Display omitted] •PEG-DMA was incorporated in unilamellar liposomes.•PEG-DMA was used to modify the aqueous core of liposomes in a hydrogel.•The arrangement of PEG-DMA within the vesicles depends on its molecular weight.•The effect of PEG-DMA on the properties of liposomes depends on its molecular weight.•Polymer inside the vesicles modifies the release properties. Since the application of nanotechnology to drug delivery, both polymer-based and lipid-based nanocarriers have demonstrated clinical benefits, improving both drug efficacy and safety. However, to further address the challenges of the drug delivery field, hybrid lipid-polymer nanocomposites have been designed to merge the beneficial features of both polymer-based and lipid-based delivery systems in a single nanocarrier. Within this scenario, this work is aimed at developing novel hybrid vesicles following the recent strategy of modifying the internal structure of liposomes. Specifically, polyethylene glycol-dimethacrylate (PEG-DMA, molecular weight 750 or 4000), was entrapped within unilamellar liposomes made of hydrogenated soybean phosphatidylcholine/cholesterol, and photo-crosslinked, in order to transform the aqueous inner core of liposomes into a soft and elastic hydrogel. After appropriate optimization of the preparation and gelation procedures, the primary objective of this work was to analyze the effect of the molecular weight of PEG-DMA on the main properties of these Gel-in-Liposome (GiL) systems. Indeed, by varying the molecular weight of PEG-DMA also its hydrophilic/lipophilic balance was modified and different arrangements of the polymer within the structure of liposomes as well as different interaction with their membrane were obtained. Both polymers were found in the inner core of the liposomes, however, the more hydrophobic PEG750-DMA also formed localized clusters within the liposome membrane, whereas the more hydrophilic PEG4000-DMA formed a polymeric corona on the vesicle surface. Preliminary cytotoxicity studies were also performed to evaluate the biological safety of these GiL systems and their suitability as innovative materials drug delivery application.