Designing microcapsules with polymer-phase change material composite shells for controlled release

Abstract

The dissertation reports a development of smart microcapsules as drug carriers and temperature microsensors for biomedical applications. The microcapsule refers to a micrometer (10-6 m) scaled spherical structure with a uniform shell surrounded it. In this study, a microfluidic device constructed with an alignment of chemically treated glass capillaries is utilized for water-in-oil-in-water (W/O/W) double-emulsions production. By controlling the flowrates of immiscible fluids in a microfluidic device, double-emulsions were fabricated in uniform sizes. Through photo-polymerization of the middle oil phase of as-prepared double-emulsions, microcapsules were fabricated in a controlled manner. When additional size reduction or high concentration of core is required, osmotic-pressure-mediated water extraction from the core of double-emulsions were additionally conducted. In order to provide thermo- and light-responsive behavior to microcapsules, the core and the membrane is designed with photothermal agents, polydopamine nanoparticles, and phase change materials (PCMs), respectively. More importantly, the membrane of microcapsules was comprised of both photocurable polymer and PCM where can create PCM channels within the crosslinked polymeric framework. Therefore, PCM can exist within the membrane upon multiple temperature swings. Since the PCM melts or freezes upon heating and cooling over or under the melting point of PCM, its state changes depend on the temperature. At a high temperature, molecular permeation differed depend on the partition coefficient between water and a liquid PCM, which was confirmed through fluorescence molecules permeation difference. Therefore, microcapsules with polarity-selective permeability was verified. Moreover, at a low temperature where makes a solid PCM, every permeation was significantly suppressed resulting thermo-responsive permeability of the membrane. Furthermore, by generating microcapsules encapsulating anticancer drugs with a high concentration, thermo- and light-responsive drug release behavior were confirmed. The cell and animal experiments were also conducted to show synergistic chemo-photothermal therapy. In addition, capsule-type microsensor was developed by introducing a thermochromic leuco dye into the PCM in the membrane to detect localized temperatures with color changes. Therefore, the microcapsules with polymer-PCM composite shells were successfully developed which are promising platform as advanced drug carriers enabling localized and sustained release of drugs on demand.