Self-assembly Behavior Of Silk Fibroin And Its Application In Drug Controlled Release

Silk has been studied enthusiastically by human for centuries mainly because of its good permeability, fairly hygroscopic, comfortable touch sensibility, unique luster and excellent mechanical properties. In recent years, extensive studies have been carried on the application of silk fibroin(SF) from traditional fabric and clothing area to biomedical areas. Silkworm fibroin has been applied in wound covering materials, surgical suture, tissue engineering and controlled release carrier, etc because of its excellent biodegradability and biocompatibility.Silk fibroin can be processed into various of forms including fibers, membranes, gels, microspheres and porous materials and so on, which are convenient for kinds of application. As carriers for drugs or gene materials, nano- and micro-systems are in favor of controlling materials release, so it is of great value in intensive studies of nano- and microspheres. Preparing SF microspheres by self-assembling is one of the most active research areas because most of human diseases are related to protein misfolding. Molecular self-assembly was the process that intermolecular form molecular aggregates with a clear structure, stable and specific property; controlled release drug system referred that the release was in zero order or nearly constant speed release under the controlled carriers in order to get a stable concentration of blood drug in the body.In this thesis, it is revealed that silk fibroin formed ordered structure of microspheres and porous scaffolds materials by self-assembling under specific condition, and the process is simple, without touching toxic organic solvents, etc. Based on the work mentioned above, we studied the application of SF microspheres and porous scaffolds in drug release primarily, such as the controlled release of drug loaded SF microspheres and porous scaffolds.In the study, we explored the process of SF microspheres formed by self-assembling under synergy of PEG and Tween-20 in freezing condition. We adopted scanning electron microscopy(SEM), atomic force microscopy(AFM),dynamic scattering, laser particle size analyzer, fourier transform infrared(FTIR) spectroscopy to characterize the morphology, particle size and formation of SF microspheres. Investigation results showed the ordered structure, excellent dispersibility and stability of microspheres could be formed under a relatively simple preparation condition, and SF microspheres with the excellent morphology and a controllability size range from 500 to 2000 nm were prepared by adjusting the concentration of silk fibroin, additive amount of inducer, stabilizer, dispersing agent and so on.SF porous scaffolds formed by self-assembling under specific condition, and forming process consisted of preparing template, SF solution casting and protein conformation transition under specific condition. Polystyrene(PS) were used to construct a ordered template, controllable porous structure and high mechanical strength of SF porous scaffolds were fabricated successfully through the infiltration of SF solution and dissolution of microspheres template. In our study, SF porous scaffolds were prepared with a controllable pore size of 2 μm and a porosity of more than 80%, and the effect of silk fibroin concentration and n-butanol additives on SF porous scaffolds’ morphology and formation were also investigated.Based on the work mentioned above, we studied simply the possibility of silk fibroin microspheres and porous scaffolds in drug release. We used SF microspheres and porous scaffold to load Doxorubicin Hydrochloride respectively, and we also investigated the property and mechanism of drug release. Investigation results showed that not only the time of drug release was longer, but also the side effects of drug loaded reduced significantly in living body and improved the efficiency of the drug.In conclusion, this work provided a way to prepare SF microspheres and porous scaffolds by silkworm fibroin self-assembling, and we also investigated the application of SF microspheres and porous scaffolds in biomedical areas, investigation results show that the release of drug loaded SF microspheres in vivo and the application of drug loaded porous scaffolds in tissue repair based on silk fibroin has an excellent application prospect in drug release.