Advanced subcompartmentalized microreactors: Polymer hydrogel carriers encapsulating polymer capsules and liposomes

The design of compartmentalized carriers for advanced drug delivery systems or artificial cells and organelles is of interest for biomedical applications. Herein, a polymer carrier microreactor that contains two different classes of subcompartments, multilayered polymer capsules and liposomes, is presented. 50 nm-diameter liposomes and 300 nm-diameter polymer capsules are encapsulated into a larger polymer carrier capsule, demonstrating control over the spatial positioning of the subcompartments, which are either 'membrane-associated' or 'free-floating' in the aqueous interior. Selective and spatially dependent degradation of the 300 nm-diameter subcompartments (without destroying the structural integrity of the enzyme-loaded liposomes) is also shown, by performing an encapsulated enzymatic reaction using the liposomal subcompartments. These findings cover several important aspects toward the development of engineered compartmentalized carrier vessels for the creation of artificial cell mimics or advanced therapeutic delivery systems. The assembly of a polymer capsule microreactor containing subcompartments of different composition, polymeric capsules and liposomes, is reported. Control over the position of the subcompartments is demonstrated, the polymeric subunits are selectively degraded, and cargo functionality is preserved within the liposomal subunits, as demonstrated through enzymatic reactions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Engineering Advanced Capsosomes: Maximizing the Number of Subcompartments, Cargo Retention, and Temperature-Triggered Reaction

Advanced mimics of cells require a large yet controllable number of subcompartments encapsulated within a scaffold, equipped with a trigger to initiate, terminate, and potentially restart an enzymatic reaction. Recently introduced capsosomes, polymer capsules containing thousands of liposomes, are a promising platform for the creation of artificial cells. Capsosomes are formed by sequentially layering liposomes and polymers onto particle templates, followed by removal of the template cores. Herein, we engineer advanced capsosomes and demonstrate the ability to control the number of subcompartments and hence the degree of cargo loading. To achieve this, we employ a range of polymer separation layers and liposomes to form functional capsosomes comprising multiple layers of enzyme-loaded liposomes. Differences in conversion rates of an enzymatic assay are used to verify that multilayers of intact enzyme-loaded liposomes are assembled within a polymer hydrogel capsule. The size-dependent retention of the cargo encapsulated within the liposomal subcompartments during capsosome assembly and its dependence on environmental pH changes are also examined. We further show that temperature can be used to trigger an enzymatic reaction at the phase transition temperature of the liposomal subcompartments, and that the encapsulated enzymes can be utilized repeatedly in several subsequent conversions. These engineered capsosomes with tailored properties present new opportunities en route to the development of functional artificial cells