The targeted delivery to specific locations while not causing damage to healthy tissues efficiently remains a challenge in drug delivery systems. Through addressing this issue, stimuli‐responsive materials have been under investigation. As one of the fundamental forces associated with blood flow, shear stress is taken as an advantage to design shear‐sensitive drug carriers. Although blood flow is modeled as laminar flow under normal conditions, in case of constrictions caused by endothelial shear stress, cardiovascular diseases, or angiogenesis due to tumor formation, local shear stress can dramatically increase. To date, shear‐sensitive materials have been investigated under two main categories: shear‐disaggregated and shear‐deformed nanoparticles based on their structural mechanism after exposure to high‐shear stress. Among them, liposomes are promising materials with their soft and deformable structure, high biocompatibility, controlled‐release properties, and sensitivity to shear stress. Herein, in this review, the effects of shear stress on liposomes in terms of their structural changes, flow regimes, rheological properties, and drug delivery applications are discussed. It is believed that this work provides a basis for designing more effective drug delivery systems considering the complexity of the human body.

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.

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.

Giant unilamellar vesicles (GUVs), soft cell‐sized compartments formed through the self‐assembly of lipid molecules, have long been utilized as model systems and passive carriers in membrane biophysics and biomedical applications. However, their potential as dynamically responsive and motile systems remains largely untapped due to challenges in achieving controlled and sustained motion in soft, deformable structures. Here, an autonomous cell‐like microrobot through the emergent self‐assembly of GUVs (5‐10 µm) and silica microparticles (1‐3 µm) under alternating current electric fields is realized. Self‐propulsion arises from asymmetric self‐organization of the particles on the vesicle surface, enabling a reversible transformation of the assembly into an active structure. Unlike rigid colloidal systems, GUVs introduce unique features enabled by their soft lipid membranes: shape deformations, membrane tension‐dependent motility, and field‐triggered live bacteria release via vesicle bursting. Through experiments and simulations, the mechanisms underlying self‐assembly and propulsion are investigated, and a dynamic phase diagram is constructed to map the motion regime as a function of field parameters. Finally, it is shown that these self‐assembled structures are capable of reconfiguration in response to local constraints in the environment, suggesting potential applications in complex environments and advancing the potential of GUVs toward the rational design of cell‐like microrobots or artificial cell systems.