Cationic lipid-coated bPEI/pDNA complexes: Correlation between physicochemical and morphological properties

Cationic lipid–polymer hybrid nanoparticles (cLPHNPs) complexed with nucleic acids, also named lipopolyplexes, have been developed as an alternative to nonviral vectors. These core/shell structures have been introduced to mitigate the limitations of cationic liposomes and biodegradable polymeric nanoparticles (NPs). The colloidal study of hybrid structures opens interesting perspectives for developing novel carriers for drug and gene delivery applications. Morphology aspects (size, lamellarity, and nucleic acid localization) and physicochemical properties of nonviral vectors influence gene delivery. Unraveling the structure of lipopolyplexes can enable their rational design toward enhanced gene delivery. Herein, we investigated the cationic LPHNPs loading plasmid DNA (pDNA) structure using dynamic light scattering, cryo-TEM, and pDNA accessibility assay. This study used pDNA as a genetic cargo for association with a cationic polymer, branched polyethylenimine (bPEI). It was found that the morphology of cationic LPHNP structures is influenced mainly by the formation process. Cationic LPHNPs formulated with EPC, DOPE, and cationic lipid DOTAP showed various degrees of multilamellarity depending on the production method. The addition of lipid dispersion to bPEI-pDNA anionic polyplex induced multilamellarity, while the preformed cationic liposome induced core/shell-like structures. Also, cLPHNPs showed better mechanical stability than polyplexes in a centrifugal vacuum concentrator (CVC) process. The physicochemical properties of cLPHNPs, formed in the presence of CL, were kept constant without significant changes. We believe these obtained colloidal data may be used to investigate hybrid-gene nanocarriers and their production process. [Display omitted]