Shear stress regulated uptake of liposome-decorated microgels coated with a poly(dopamine) shell

Advanced multicompartment drug delivery platforms ensure the co-localization of several drugs within the same carrier, thus making it possible to achieve a more effective and safe therapeutic outcome. Herein, we report a novel multicompartment architecture by combining two intrinsically different systems, i.e., polymeric microgels and liposomes, with the aim to achieve different release kinetics for model compounds. We assemble poly(N-isopropylacrylamide-co-acrylic acid) microgels decorated with liposomes which are subsequently coated with a protective poly(dopamine) shell and a poly(ethylene glycol) (PEG) layer. Since any intravenous administered drug delivery vehicle will get in contact with the dynamics of the blood flow, we evaluate the stealth properties of this novel multicompartment carrier towards protein adsorption and cellular uptake by three relevant cell lines (macrophages, endothelial and cancer cells) under physiological shear stress conditions. Our results demonstrate less protein adsorption for the PEGylated carriers and differences in the extent of internalized carriers depending on the presence of a PEG coating, the studied cell line and the intensity of the applied shear stress. Additionally, we demonstrate that, for all three tested cell lines, shear stress results in the activation of different cell entry pathways as compared to static conditions. All in all, we report a thorough study about the effect of shear stress on the cell association/uptake with a novel multicompartment carrier.