Structure-Based Evaluation of Hybrid Lipid-Polymer Nanoparticles: The Role of the Polymeric Guest

The combination of phospholipids and block-copolymers yields advanced hybrid nanoparticles through the self-assembly process in an aqueous environment. The physicochemical features of the lipid/polymer components, like the lipid-polymer molar ratio, the macromolecular architecture of the block copolymer, the main transition temperature of the phospholipid, as well as the formulation and preparation protocol parameters, are some of the most crucial parameters for the formation of hybrid lipid/polymer vesicles and for the differentiation of their morphology. The morphology, along with other physicochemical nanoparticle characteristics are strictly correlated with the nanoparticle's later biological behavior after being administered, affecting interactions with cells, biodistribution, uptake, toxicity, drug release, etc. In the present study, a structural evaluation of hybrid lipid-polymer nanoparticles based on cryo-TEM studies was undertaken. Different kinds of hybrid lipid-polymer nanoparticles were designed and developed using phospholipids and block copolymers with different preparation protocols. The structures obtained ranged from spherical vesicles to rod-shaped structures, worm-like micelles, and irregular morphologies. The obtained morphologies were correlated with the formulation and preparation parameters and especially the type of lipid, the polymeric guest, and their ratio.