Preparation Biodegradable Silk Fibroin Films Modified With Crosslinking Agent For Controlled Drug Release

Silk fibroin is a kind of natural protein polymer which is extracted from silk. It has a good application prospect in the field of tissue engineering beacause of good biocompatibility, mechanical strength and avirulent side-effect. In recent years, the preparation and application of silk fibroin obtained great development in the area of biomedical material, preparation silk fibroin material of which structure and properties can be regulated with the needs of the biomedical research has gradually become more and more meaningful, and chemical crosslinking modification is an important way to adjust the structure and properties of silk fibroin material.Firstly, Glutaraldehyde (GA) cross-linked silk fibroin (SF) films were prepared using a solution casting method and the structural change were investigated by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The results were utilized to reveal the influence of glutaraldehyde cross-linking on the mechanical and dissolution properties of SF films, and the release kinetics of Rhodamine B, a model compound loaded in the SF matrix, with the purpose to regulate the drug releasing property of SF biomaterial by cross-linking methods. The results indicated that glutaraldehyde induced conformational transition of SF from random coil to β-sheet and had influenced on the interaction between the peptide segments in noncrystalline region of SF, resulting in great changes in mechanical and dissolution properties, as well as drug release feature of the films. With increasing content of glutaraldehyde, the tensile strength and elongation of modified films first increased then decreased, reaching a maximum at glutaraldehyde content around7.5%. Glutaraldehyde cross-linking was found to increase the stability of SF films in water and greatly reduced the burst release of Rhodamine B. The release of Rhodamine B exhibited a similar behavior, an initial burst followed by a continuous, steady and linear release, of which the release rate first increased and then decreased with increasing glutaraldehyde content. Furthermore, it was found that the release rate of Rhodamine B at later stage had a good linear fit to P-sheet content in the matrix.Then, we chose macromolecular crosslinking agent-polyethylene glycol ether (PGDE) for the preparation of crosslinked silk fibroin film. The results showed that PGDE can induce conformational transition of SF from random coil to β-sheet, and when the WPGDE=10%showed high tensile strength and low flexibility. In addition, adding PGDE can greatly improve the stability of silk fibroin film in the PBS or protease ⅩⅣ, the degradation rate slowed down, and the degradation first decreased and then increased, reaching a minimum around wPGDE=10%. The drug release rate in the PBS or protease ⅩⅣ decreased with increases PGDE content, and the accumulated release rate increased linearly with time. Rhodamine B release from cross-linked silk films mainly via atypical Fickian diffusion, and caused release constant k decreased and diffusion parameter n increased with increasing PGDE content. It was suggested that Rhodamine B released from silk fibroin films maybe due to the matrix dissolution and degradation factors, and controlled by the particle size, the crystal structure of silk fibroin films, the diffusion of the drug molecules and matrix swelling. This can provide us the necessary experimental and theoretical basis to the release and degradation mechanism of silk fibroin biomedical materials, which will be useful in the design and application of silk fibroin.