A dual-component carrier with both non-enzymatic and enzymatic antioxidant activity towards ROS depletion.

While ROS display crucial functions in many physiological processes, elevated ROS levels are also related to the initiation and progression of many severe diseases such as cancer, cardiovascular conditions or neurologic disorders. Research approaches to diminish ROS levels during disease progression are currently being focused on the therapeutic administration of antioxidant enzymes. However, enzyme administration suffers from several limitations including their fast elimination from blood upon administration, thus making crucial the development of enzyme encapsulating platforms. We have recently reported a multicompartment architecture constituted by two inherently different types of materials, i.e., polymeric microgels and liposomes. Poly(N-isopropylacrylamide-co-acrylic acid) microgels decorated with liposomes and subsequently coated by a protective poly(dopamine) shell (PDA) combine the benefits of both systems while minimizing some of their drawbacks. Herein, we exploit this dual-component platform as a microreactor for ROS depletion. We combine the intrinsic PDA's antioxidant properties with the encapsulation of the catalase enzyme within the liposomal compartments. The surface of the carrier is further functionalised with a poly(ethylene glycol) layer and the low fouling properties are demonstrated in terms of reduction of protein adsorption and cellular uptake. The potential of the carrier as an antioxidant microreactor is shown by its ability to deplete superoxide radicals and hydrogen peroxide, which can also take place in the presence of the two relevant cell lines.

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.