Preparation And Characterization Of Hollow Multilayered Microcapsule And Porous Inorganic Nanoparticle As Drug Carrier

The novel drug delivery carriers have attracted extensive attention with the development of the pharmaceutics. Drug delivery carriers refer to the designed materials that could be assigned to the drug molecules to exhibit unique function in the aspect of drug loading and release without any damage to the activity of the drug molecules. In contrast with the ordinary drug carrier, novel drug delivery carriers are able to achieve the strict control of the spatio-temporal characteristics of the drug delivery process, sequentially conquer a series of physiological drawbacks such as intercellular and intracellular degradation, improper tissue diffusion and the difficulty about passing through cell membrane, and eventually realize the delivery of appropriate dose of drug molecules to the targeted site at a proper time.Chapter 1 summarized the function of the novel drug delivery carriers, the fundamental and applications of which are introduced as well as the recent progresses. The hollow multilayered microcapsule and the inorganic nanoparticle used as drug delivery carriers are detailedly introduced and compared with their advantages and limitations.In chapter 2, two kinds of polycation with or without repeating disulfide linkage in the main chains were synthesized. Calcium carbonate microspheres were prepared and characterized by scanning electron microscope (SEM). The microspheres were turned out to be monodispersed pellets with a diameter about 5μm and have a rough porous surface. Synthesized polycation and PSS were used to fabricate multilayer on the surface of the microspheres through the layer-by-layer assembly. Hollow microcapsules were gained following the removal of the calcium carbonate core. The alternating positive and negative changes of the surface potential owe to the alternating polyelectrolyte deposition was traced. The morphology of the microcapsules was characterized by the SEM and CLSM. It was observed that the hollow microcapsules were about 5μm in diameter and had a rough but compact shell. The release of the FITC-dextran from the hollow microcapsules w as determined by the fluorescent spectra. It was confirmed that the disulfide bond contained microcapsules could release the encapsulated materials in responding to the reductive environments. The release behavior of the microcapsules modulated by the change of the component of the shell was studied and confirmed by SEM and fluorescent spectra.In chapter 3, we developed a method of preparing porous iron oxide nanoparticles. The morphology and the structure of the so-synthesized PION were investigated by TEM, nitrogen adsorption-desorption analysis, etc. The crystallinity and phase information for the PION are provided by the corresponding XRD pattern. The PION was turned out to be the nanoparticles that mainly composed by the pure rhombohedralα-Fe2O3. The PION has the size around 50nm and the slit-shaped mesopores with the pore width of 2.1-2.4nm. The anticancer drug DOX was adopted to study the loading and releasing property on the PION. Efficiently DOX adsorption was proved and the releasing speed in acidic environment was apparently faster than that in neutral environment. The cell viability assay and the investigation of the intercellular trafficking of the nanoparticles, measured by the TEM, CLSM and the ICP-AES, revealed that the PION could be efficiently internalized by the cancer cells through the endocytosis process and realize the controlled delivery of anticancer drug successfully.The morphology and the structure of the inorganic nanoparticles affect a lot to their functions. In chapter 4, we was able to change the morphology of the porousα-Fe2O3 nanoparticles based on the previous chapter and get a new kind of porous iron oxide nanorod (PIONR) by modulating the preparation method. The structure and the property of the PIONR were investigated by XRD, TEM, and nitrogen adsorption-desorption analysis, etc. The PIONR was turned out to be the nanorods that mainly composed byα-Fe2O3. The PIONR has the size about 50nm by 20nm and the slit-shaped mesopores with the pore width of 2.4nm. Efficiently DOX adsorption was proved and the release speed in acidic environment was apparently faster than that in neutral environment. The cell viability assay. as well as the investigation of the intercellular trafficking of the nanoparticles. revealed that the PIONR could be efficiently internalized by the cancer cells through the endocytosis process and realize the controlled delivery of anticancer drug successfully. In compared with PION, PIONR shows higher loading efficiency of the DOX and intracellular delivery efficiency.In chapter 5, PION and PIONR was studied about their applications in the aspect of intracellular macromolecule drug delivery system with FITC-dextran used as a template drug. Their adsorption efficiency about FITC-dextran was tested. By comparison, the PIONR could adsorb a larger amount of FITC-dextran with higher efficiency. The loading of the FITC-dextran was proved by the measure of surface potential and the FT-IR in parallel with the change of the surface potential. Cell uptake of the FITC-dextran loaded materials was studied by CLSM and ICP-AES, where the PIONR performed better than PION did. Polymer 1 was used to make a surface modification of the both two to turn back their surface potential to be positive. CLSM and ICP-AES was utilized to examine the cell uptake of the modified carriers. Extremely high cell uptake efficiency of PION and PIONR by the HeLa cells was observed, and still PIONR did a better job.