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Chimeric/mixed stimuli-responsive nanocarriers are promising agents for therapeutic and diagnostic applications, as well as in the combinatorial field of theranostics. Herein, we designed chimeric nanosystems, composed of natural phospholipid and pH-sensitive amphiphilic diblock copolymer, in different molar ratios and assessed the polymer lyotropic effect on their properties. Initially, polymer-grafted bilayers were evaluated for their thermotropic behavior by thermal analysis. Chimeric liposomes were prepared through thin-film hydration and the obtained vesicles were studied by light scattering techniques, to measure their physicochemical characteristics and colloidal stability, as well as by imaging techniques, to elucidate their global and membrane morphology. Finally, in vitro screening of the systems' toxicity was held. The copolymer effect on the membrane phase transition strongly depended on the pH of the surrounding environment. Chimeric nanoparticles were around and above 100 nm, while electron microscopy revealed occasional morphology diversity, probably affecting the toxicity of the systems. The latter was assessed to be tolerable, while dependent on the nanosystems' material concentration, polymer concentration, and polymer composition. All experiments suggested that the thermodynamic and biophysical properties of the nanosystems are copolymer-composition- and concentration-dependent, since different amounts of incorporated polymer would produce divergent effects on the lyotropic liquid crystal membrane. Certain chimeric systems can be exploited as advanced drug delivery nanosystems, based on their overall promising profiles.

Different in nature biomaterials, which are used for the development of drug delivery nanosystems, could be mixed, in order to produce chimeric/mixed nanostructures. Their morphological characteristics and biophysical properties depend on the degree of association and interactions between the self-assembling biomaterials. For the purpose of this study, chimeric nanosystems composed of phospholipid and amphiphilic diblock copolymers were developed, at different molar ratios. Light scattering and imaging techniques were employed, in order to extract information on the nanostructure physicochemical characteristics and their morphology. Certain morphological characteristics were assessed for vesicle membranes, which are considered to be of paramount importance for their fate inside the physiological environment and their biophysical behavior. Besides vesicles, a variety of structures appeared in the phospholipid/copolymer chimeric systems, depending on both the composition and the concentration of the utilized polymer, declaring the lyotropic effect on the self-assembly of the biomaterials. The size range of most objects, including vesicles, was around 100 nm. Membrane irregularities, such as domains and rafts, are considered as functional biophysical factors, rendering liposomes appropriate artificial models for approaching various diseases on the level of living cell membranes. Such information is of paramount importance for the utilization of chimeric nanostructures in drug delivery and in therapy.