Smart amphiphilic copolymers as building blocks for hybrid lipid-copolymer systems and devices

Lipid membranes are ubiquitous biological motifs that play a crucial role in the compartmentalization of functional cell components. They consist of lipid bilayers that have inspired a variety of synthetic architectures for bio-applications. The molecular building blocks of bilayers, lipids, are amphiphilic and show selfassembly behavior in solution. Amphiphilicity is very common in biomacromolecules but can also be engineered in synthetic alternatives, like amphiphilic copolymers. They spontaneously self-assemble in similar aggregates, yielding new properties to the whole system. In recent years, advanced systems derived from both amphiphilic scaffolds have raised new geometries for engineering improved composite materials. This work addresses the design and characterization of hybrid lipid-polymer systems arranged in lamellar or non-lamellar assemblies for two primary purposes: i) the development of innovative biomimetic platforms and ii) the design of intelligent stimuli-responsive lipid-based nanoparticles (NPs). The first part discusses the realization of an innovative biomimetic-platform consisting of hybrid lipid-copolymer systems assembled in lamellar structures of the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and the block copolymer poly(butadiene-b-ethyleneoxide) (PBD-b-PEO). Lateral phaseseparated lamellar structures were challenged with inorganic nanoparticles, i.e. Turkevich-Frens gold nanoparticles (AuNPs), revealing selective interaction between the small particles and the soft polymeric domains. In the second part of this work, the design and characterization of not-lamellar lipid nanoparticles stabilized by a new smart copolymer were addressed to develop a novel class of thermo-responsive drug delivery systems. Specifically, a thorough investigation of the self-assembly behavior of novel thermo-responsive dimethyl acrylamide (DMA) and N-isopropylacrylamide (NIPAM) copolymers in water is first explored. Then, the characterized thermo-responsive block copolymers were investigated as new smart stabilizers for not-lamellar lipid glycerol monooleate (GMO) nanoparticles to design highly lipophilic and stimuli-responsive drug delivery systems towards synthetic and natural membranes. In conclusion, the results of this work contribute to finely defining the physicochemical and self-assembly behavior of amphiphiles of different natures in a polar solvent and introduce the design of new biotechnological nanodevices that combine lipid bilayers and smart amphiphilic block copolymers.