RÉSUMÉ
Lipid-based vesicles, namely cationic liposomal nanocarriers have been recognized early on as one of the most attractive delivery systems for RNA, protein, and oligonucleotides. Despite several advantages of conventional liposomal carriers for therapeutic macromolecules, their flexible and unsupported bilayered membranes can pose some limitations for efficient intracellular delivery of their sensitive cargos. Hence, polymerized liposomes, a concept conceived about 20 years ago, might offer structural solution to current in vivo efficiency concerns affecting traditional cationic phospholipid vectors, especially when adapted to enable superior loading and stability, typically required for effective intracellular delivery of proteins and polynucleotides.Our recent approach attempted to remodel polymerized liposomal vesicles-specifically their semi-rigid membrane structure-to create block-polymerized bilayered vesicles (generally composed of DOTAP: DOPE: Diyne PC in 0.1:1:1 molar ratio). Adopting a modified freeze-dry-rehydration technique allowed modular reassembly of such partially polymerized lipidic vesicles (PPL). Different prototype cationic partially polymerized liposomal preparations (PPLs) were successfully developed (mean particle size range 150-300 nm), demonstrating enhanced physicochemical stability and loading capacity, thus promoting improved intracellular delivery of model RNAi and protein cargos.