Colloidosomes Fabricated Through Emulsion Droplet Template Method And Their Application

The present research focuses on emulsion droplet template method, developed for preparing colloidosome. Colloid particles adsorb on the surface of the emulsion droplets and self-assemble into an ordering spherical solid shell. Cross-linking and fixing the shell, the novel capsule"colloidosome", which is composed of a close-packed shell of colloid particles, can be fabricated. Colloid particles with different size and properties have been chosen to fabricate colloidosome based on emulsion droplet template method. The self-assembled discipline of colloid particles absorded on the surface of emulsion droplet can be investigated. The technique of fabrication and the control of the size, permeability, mechanical strength of the colloidosome have been built. The effects on the structure and property of colloidosome have been researched. Further, the application of the colloidosome for controlled release of drug can also be researched. The main contents and the results of the research are as following:1. The colloidosomes with alginate gel cores and shells of porous CaCO3 microparticles were fabricated by templating water-in-oil emulsion and in-situ gelation. First porous CaCO3 microparticles with the diameter of 5μm were fabricated by the reaction of CaCl2 and NaCO3.with equal mol. The optimal condition is that the concentration of CaCl2 and NaCO3 are both 0.2M, the concentration of PSS is 4g/L and the stirring speed is 1000rpm.W/O emultions were obtained through self-assembly of CaCO3 microparticles at interface of alginate equeous solution and sun flower oil. Water droplets containing alginate in the emulsion were subsequently in situ gelated by Ca2+ released from CaCO3 through decreasing pH with slow hydrolysis of d-glucono-lactone (GDL). The resulting colloidosomes with alginate gel cores and shells of porous CaCO3 microparticles were fabricated. The core-shell structure of the colloidosome beads was proved with the combination of optical microscopy, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM).The self-assembled discipline of porous CaCO3 microparticles absorded on the surface of emulsion droplet can be investigated by varying emulsion type, ratio of particle weight to disperse phase volme (MP/Vd), volume fraction of water and NaCl concentration. The results are that the packed density of CaCO3 microparticles in the shell increased with increasing the ratio of the CaCO3 microparticle weight to the water phase volume MP/Vd and decreased with addition of NaCl into water. When MP/Vd = 0.03 g/mL, the CaCO3 microparticles were not closely packed and the alginate gel core was not completely covered with CaCO3 microparticles. When MP/Vd = 0.04 g/mL, almost close-packed shell of CaCO3 microparticles was formed. When MP/Vd = 0.05 g/mL, a close-packed CaCO3 microparticle shell was found with many CaCO3 microparticle aggregates on the surface. With adding 0.5 and 1.0M of NaCl into the aqueous alginate solution, the CaCO3 microparticles aggregated and the uncovered area on the gel core surface increased. The stability of the colloidosome decreased with increasing the volume fraction of water. WhenΦd = 0.2, the colloidosome was stable with spherical shape. There was almost no coalescence in the emulsion. WhenΦd = 0.3, some colloidosomes coalesced, but they were stable with spherical shape. IncreasingΦd to 0.5, we found deformation of some colloidosomes to non-spherical shape and even broken for some colloidosomes.The result of diameter distribution of these colloidosomes showed that the colloidosome diameter ranged from tens to 900μm with an average diameter of 430μm. The size of the droplets is solely determined by the input of mechanical energy during emulsification and is independent of MP/Vd.2. Based on emulsion droplet template method, Well-defined magnetic nanocomposite colloidosome beads with alginate gel cores and shells of iron oxide (γ-Fe2O3) nanoparticles were prepared by self-assembly of colloidal particles at liquid-liquid interfaces and subsequent in-situ gelation. The core-shell structure of the colloidosome beads was proved with the combination of optical microscopy, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). The structure of the colloidosome is so stable that it can be saved for long time and still keep its origin shape which is the result of the exist of alginate gel cores and shells of iron oxide (γ-Fe2O3) nanoparticles. At the same time, the colloidosome with alginate gel cores and shells of iron oxide (γ-Fe2O3) nanoparticles are magnetic. The diameter distribution of the colloidosome was also polydispersion and the mean diameter is 135μm, which was lower than the CaCO3-ALG colloidosome resulted from the exist of Fe2O3 nanoparticles.3. Based on emulsion droplet template method we present a facile novel fabrication method for magnetic flexible microcapsules with inorganic/polymer composite shell by self-assembly of colloidal particles at liquid-liquid interfaces and subsequent radical polymerization at high temperature which can be named Pickering emulsion polymersion. Fe2O3 nanoparticles spontaneously adsorbed to the water droplet surfaces to stabilize water-in-hexane emulsions. Water droplets containing N-isopropylacrylamide and initiator subsequently polymerized at 60oC. Because of the hydrophobicity of the obtained poly-N-isopropylacrylamide macromolecule, it was deposited from inter water phase on the interface and formed Fe2O3 nanoparticles/poly-N-isopropylacrylamide composite shell. We used optical microscope, confocal laser scan microscopy and scan electron microscope to prove that the structure of hollow microcapsules with Fe2O3 nanoparticles/PNIPAm composite shell.In addition, we also discussed the magnetism, return performance and thermo-sensitive properties of hollow microcapsules we obtained. The result showed that the hollow microcapsules appeared magnetic, good return performance and good permeability and thermo-sensitive properties.4. Brilliant blue (BB) as a drug model was loaded into the colloidosome beads with alginate gel cores and shells of porous CaCO3 microparticles by being dissolved in the alginate aqueous solution before gelation. BSA as water-soluble protein drug was loaded into the colloidosome beads with alginate gel cores and shells of iron oxide (γ-Fe2O3) nanoparticles by being dissolved in the alginate aquous solution before gelation. Insulin microcrystals as water-nonsoluble drug were encapsulated into colloidosome beads with alginate gel cores and shells of iron oxide (γ-Fe2O3) nanoparticles by dispersing them in the alginate sodium aqueous solution in the colloidosome fabrication process. The sustained release of BB, BSA and Insulin microcrystals could be obtained in model release medium due to the advantage of two levels of encapsulation of alginate gel cores and shells of porous CaCO3 microparticles or Fe2O3 nanoparticles. Meanwhile the whole release curves were respectivelly fitted by Monoexponential equation, Higuchi equation, the Weibull equation and Hixson-Crowell equation. We find that the Weibull equation can nicely explain the release mechanism of the above release system. The fitted results of the Weibull equation proved that the drug release from the colloidosomes followed Fick diffusion.