Fabricating hybrid DSPC:DOPC:P(OEGMA-co-LMA) structures: Self-assembly as the milestone of their performance.

Lipid/polymer nanoparticles are among the most promising hybrid nanoplatforms for pharmaceutical applications, and their many advantages are well established. Despite the efforts, the design parameters that influence their performance have not been deciphered in total yet. In this study, thermodynamic evaluation of lipid and lipid/copolymer bilayers was conducted via differential scanning calorimetry (DSC). Based on their biophysical behavior and by modulating different design parameters for each system, selected lipid/copolymer nanostructures were prepared by the thin film hydration method. The biomaterials of choice were 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and a linear statistical (random) copolymer comprised of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and lauryl methacrylate (LMA). Their features were examined by light scattering techniques, fluorescence spectroscopy, and MTS assay. For the first time DSPC:DOPC:P(OEGMA-co-LMA) hybrid systems were successfully formulated and the most prominent factors influencing their thermodynamic, physicochemical, and toxicological properties were investigated. Our results indicate that self-assembly is pivotal for hybrid systems performance and is mediated via random topology of copolymer, lipid composition, hydrophilic to hydrophobic balance, and lipid to polymer ratio. Having in mind fast clinical translation, we hope this work to contribute to a design road map for efficient lipid/copolymer nanostructure development. [Display omitted] [ABSTRACT FROM AUTHOR]