Viscoelastic effects on structure and dynamics of liposomes in polymeric matrices

Recent decades have seen significant advancements in the pharmaceutical industry and nanotechnology, which have led to the development of clinical research and the discovery of modern drug delivery methods. As one of the widely used nanoparticles, liposomes are employed in pharmaceutics, tissue engineering, cell membrane modelling, cosmetics, and agriculture with their high biocompatibility, biodegradability, low toxicity, and resemblance to biological membranes. Although liposomes offer serious advantages, they have drawbacks such as their thermodynamically unstable structure, quick elimination in the bloodstream, and a desire to targeted and dosage-controlled delivery. To overcome these issues, the combination of liposomes with polymer solutions, and hydrogels have been utilized since polymers provide mechanical support, stimuli-responsive release, and increased stability towards chemicals, enzymes, and immune systems. Besides, polymeric scaffolds can be designed to mimic the topology and mechanical characteristics of the native extracellular microenvironment. Although there is a great deal of interest in liposome-polymer complexes from the application point of view, the effects of viscoelasticity of polymers on liposome structure, permeability, and mobility need detailed understanding. This thesis contains two different studies on liposomes and Polyethylene glycol (PEG) mixtures. In the first one, we used 100 nm unilamellar DMPC/DMPG liposomes, and aqueous solutions of poly (ethylene glycol) (PEG) with various molecular weights from 1.5 kDa to 400 kDa to simulate the viscous media of cells. The structural phase map and multiscale dynamics of liposomes in their neat form and in the presence of PEG solutions were investigated. The findings point to a dynamical coupling at various length/time scales between polymer chains and phospholipid bilayers. The relaxation of the entire chain directly affects the microviscosity of the lipid bilayers, which causes faster dynamics of the lipids within the bilayers when compared to the polymer-free liposome case. We observed a thermal-thickening behaviour of polymer-liposome solutions at the transition temperature of the lipids from gel to fluid, which is tuneable by the concentration of liposomes and the length of the polymer chain. In the second study, we used unilamellar 100 nm DMPC/DMPG liposomes and PEG hydrogels having different elasticities, from 1 Pa to 180 Pa, and created a composite hydrogel. We studied the release of liposomes from the ECM-mimetic gel matrices under quiescent and shear deformation. The presence of liposomes provides composite hydrogels with temperature-controlled swelling capacity that is sensitive to membrane microviscosity. By systematically varying shear deformation from linear to nonlinear regimes, we studied the effect of shear deformation on the release of liposomes from the hydrogels of different stiffness.