Multicompartment polymersomes from double emulsions.

Polymersomes are vesicles which consist of compartments surrounded by membrane walls that are composed of lamellae of block copolymers. They are important for numerous applications in encapsulation and delivery of active ingredients such as food additives, drugs, fragrances, and enzymes. Polymersomes are typically prepared by precipitating block copolymers from their solvents through addition of a poor solvent for the copolymers, or by rehydrating a dried film of the copolymers. The unfavorable interactions between blocks in the copolymer and the poor solvent induce formation of aggregate structures ranging from micelles, wormlike micelles, and vesicles. However, the resultant polymersomes are highly polydisperse and have poor encapsulation efficiency. Recently, a new approach has been developed to fabricate monodisperse polymersomes by using double emulsions as templates. Water-in-oil-in-water (W/O/W) double emulsions with a core–shell structure are first prepared in capillary microfluidic devices. Diblock copolymers, dissolved in the oil shell phase, assemble into the walls of the polymersomes upon removal of the oil by evaporation after adhesion of the diblock copolymeradsorbed interfaces. This approach leads to polymersomes with high size uniformity and excellent encapsulation efficiency and also enables precise tuning of the polymersome structures. Advances in techniques for fabricating polymersomes have led to controlled spherical polymersomes with a single compartment. However, non-spherical capsules with multiple compartments also have great potential for encapsulation and delivery applications. By storing incompatible actives or functional components separately, polymersomes with multiple compartments can achieve encapsulation of multiple actives in single capsules and reduce the risk of crosscontamination. Moreover, multiple reactants can be encapsulated separately to allow reaction upon triggering. By tuning the number of compartments containing reactant, the stoichiometric ratio of the reactants for each reaction can be manipulated. These multicompartment polymersomes will create new opportunities to deliver not only multiple functional components, but also multiple reactants for reactions on demand. In addition, with the versatility of synthetic polymer chemistry to tune properties such as polymer length, biocompatibility, functionality, and degradation rates, nonspherical polymersomes with multiple compartments can be tailored for specific delivery targets. However, polymersomes that have been reported to date are almost exclusively spherical in shape, and have only one compartment. Since most conventional polymersome fabrication processes rely on self-assembly of the block copolymer lamellae, little control over the size and structure of the resultant polymersomes is achieved. With the conventional emulsion-based methods, non-spherical droplets are also not favored because interfacial tension between the two immiscible phases favors spherical droplets, which have the smallest surface area for a given volume. Recent advances in microfluidic technologies enable high degree of control in droplet generation, and ease in tuning the device geometry. This offers a new opportunity to fabricate double emulsion with controlled morphology, which serve as templates for fabricating the non-spherical multicompartment polymersomes. However, such investigations have not, as yet, been carried out. Here, we demonstrate the generation of non-spherical polymersomes with multiple compartments. We use glass capillary microfluidics to prepare W/O/W double emulsions with different number of inner aqueous drops. These emulsions are initially stabilized by the amphiphilic diblock copolymers in the oil shells, which consist of a mixture of a volatile good solvent and a less volatile poor solvent for the copolymers. As the good solvent evaporates, the copolymers at theW/O and the O/W interfaces are attracted towards each other to form the membranes. As a result, neighboring inner droplets adhere to one another and this leads to formation of multicompartment polymersomes, as illustrated in Scheme 1. We also use a modified glass capillary device for generating double emulsions with two distinct inner phases containing different encapsulants. This process leads to the fabrication of non-spherical polymersomes with multiple compartments for separate encapsulation of multiple actives. A glass capillary microfluidic device is used to generate double emulsions with controlled morphology (see Figure S1 in the Supporting Information). Due to the high degree of control afforded by microfluidics, the number of inner droplets in a W/O/W double emulsion system can be controlled by varying the flow rates of the three phases independently. An example of the process is shown in Figure 1a. The thickness of the double emulsion shells can be adjusted by changing the flow rates. However, as long as the flow rates are not altered enough to change the number of [*] Dr. H. C. Shum, Y. J. Zhao, Dr. S. H. Kim, Prof. D. A. Weitz School of Engineering and Applied Sciences, Department of Physics and Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, MA 02138 (USA) E-mail: [email protected] Homepage: http://www.seas.harvard.edu/projects/weitzlab/