Design and development of DSPC:DAP:PDMAEMA-b-PLMA nanostructures: from the adumbration of their morphological characteristics to in vitro evaluation

In this study, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-3-dimethylammonium-propane (DAP) and amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PLMA-b-PDMAEMA) in the weight ratios: 1:0:0.03, 1:0.1:0.03, 1:0.3:0.03, 1:0.5:0.03, 1:0.7:0.03, and1:1:0.03, were used for the design and development of hybrid polymer-lipid nanostructures. The polymer-lipid nanostructures were prepared using the aqueous heat method. The pure lipid systems were used as reference systems. Differential Scanning Calorimetry (DSC) was utilized to investigate the interactions between the components. The presence of the polymeric guest caused different orientation of the polar groups of phospholipids, as the DSC thermotropic values revealed. The changes of the physicochemical characteristics of the systems with the increase of the weight ratio of DAP are more intense in comparison to those without this lipid due to the presence of the block copolymer, which contributes significantly to the repulsive interactions between the vesicles as a result of its positive charge. The only exception is the DSPC:DAP:PLMA-b-PDMAEMA nanosystem at 1:0.5:0.03 wt ratio, where the size of the polymer/lipid structures (Dh≈320 nm) increased and the ζ-potential decreased in absolute values in comparison with the systems with lower weight ratio of the DAP lipid. Cryogenic Transmission Electron Microscopy (cryo-TEM) images showed different structures which strongly depend on the composition of the system, ranging from lamella structures, disc forms, and “spaghetti” morphologies. Based on toxicity studies, it was found all samples are biocompatible and show a dose-dependent cytotoxicity on HEK293 (Human Embryonic Kidney 293 cell line). In conclusion, we developed polymer/lipid nanostructures with knowledge of their structural and physicochemical characteristics, useful as drug or antigen delivery platforms. © 2021