Microfluidic Fabrication of pH-Responsive Microcapsules via Interfacial Complexation of Hydrogen-Bonding Polymers

MasterStimuli-responsive controlled release system has received significant attention due to its ability to effectively deliver drugs to target site by sensing the local environment within the body. These systems respond to various stimuli such as temperature, pH, light, etc. and allow on-demand release of the encapsulated cargoes. For instance, when a polymer sensitive to pH is applied to a microcapsule, the drug encapsulated within the capsule can be selectively delivered to the tumor site or wound tissue, which exhibit different pH than the surrounding. While various pH-sensitive microcapsules have been reported up to now, a versatile strategy that allows preparation of pH-responsive microcapsules with well-defined size and shape in a continuous manner still remains a problem to be resolved. In this study, a microfluidic approach in which water-in-oil-in-oil-in-water (W1/O1/O2/W2) triple emulsion droplets are used as templates to produce uniform pH-responsive microcapsules, is presented. Two polymers capable of forming hydrogen-bonding complex each exist in W1 and O2 phase, respectively, while an additional oil phase (O1) without polymer is present between these two phases serving as a buffer layer. Unlike conventional double emulsion approach, the presence of the buffer layer in triple emulsion enables the droplet formation and the hydrogen-bonding complex formation process to be decoupled, reducing the chance of device clogging and thus offers stable production of microcapsules. We also show that the complexation occurs immediately after droplet formation and that the remaining oil layer ruptures upon contact with the water/air interface to result in hydrogen-bonded microcapsules, directly dispersed in water. Moreover, we show that these hydrogen-bonded microcapsules can stably store at low pH while the complex can be dissolved above a certain pH to release the encapsulated cargo. Furthermore, we believe that the strategy outlined in this work is applicable to a broad range of polymers with different pKa values, presenting a new direction in the design of pH-responsive microcapsules