Shear-Triggered Release of Lipid Nanoparticles from Tissue-Mimetic Hydrogels.

Shear forces are involved in many cellular processes and increase remarkably in the case of cardiovascular diseases in the human body. While various stimuli, such as temperature, pH, light, and electromagnetic fields, have been considered for on-demand release, developing drug delivery systems that are responsive to physiological-level shear stresses remains as a challenge. For this purpose, liposomes embedded in hydrogel matrices are promising as they can dynamically engage with their environment due to their soft and deformable structure. However, for optimal drug delivery systems, the interaction between liposomes and the surrounding hydrogel matrix, and their response to the shear should be unraveled. Herein, we used unilamellar  1,2-Dimyristoyl-sn-glycero-3phosphocholine (DMPC) liposomes as drug nanocarriers and polyethylene (glycol) diacrylate (PEGDA) hydrogels having different elasticities, from 1 to 180 Pa, as extracellular matrix (ECM)-mimetic matrices to understand shear-triggered liposome discharge from hydrogels. The presence of liposomes provides hydrogels with temperature-controlled water uptake which is sensitive to membrane microviscosity. By systematically applying shear deformation from linear to nonlinear deformation regimes, the liposome release under transient and cyclic stimuli is modulated. Considering that shear force is commonly encountered in biofluid flow, these results will provide fundamental basis for rational design of shear-controlled liposomal drug delivery systems.

Multiscale Dynamics of Lipid Vesicles in Polymeric Microenvironment.

Understanding dynamic and complex interaction of biological membranes with extracellular matrices plays a crucial role in controlling a variety of cell behavior and functions, from cell adhesion and growth to signaling and differentiation. Tremendous interest in tissue engineering has made it possible to design polymeric scaffolds mimicking the topology and mechanical properties of the native extracellular microenvironment; however, a fundamental question remains unanswered: that is, how the viscoelastic extracellular environment modifies the hierarchical dynamics of lipid membranes. In this work, we used aqueous solutions of poly(ethylene glycol) (PEG) with different molecular weights to mimic the viscous medium of cells and nearly monodisperse unilamellar DMPC/DMPG liposomes as a membrane model. Using small-angle X-ray scattering (SAXS), dynamic light scattering, temperature-modulated differential scanning calorimetry, bulk rheology, and fluorescence lifetime spectroscopy, we investigated the structural phase map and multiscale dynamics of the liposome-polymer mixtures. The results suggest an unprecedented dynamic coupling between polymer chains and phospholipid bilayers at different length/time scales. The microviscosity of the lipid bilayers is directly influenced by the relaxation of the whole chain, resulting in accelerated dynamics of lipids within the bilayers in the case of short chains compared to the polymer-free liposome case. At the macroscopic level, the gel-to-fluid transition of the bilayers results in a remarkable thermal-stiffening behavior of polymer-liposome solutions that can be modified by the concentration of the liposomes and the polymer chain length.