Preparation And Properties Of Cellulose Nanofibers-based Indomethacin Composite Fibers And Biological Scaffolds Of Bovine Serum Albumin

Cellulose nanofibers (CNFs) are natural macromolecule biomaterials, which have prospective properties such as large specific surface area, strong hydroxyl group activities, fine structure, and easy chemical modification, non-toxicity, biocompatibility, self-assembly and so on. CNFs are a kind of ideal drug carrier polymer materials. With the development of nanotechnology, the structure and properties of CNFs have gotten a lot of research and attention, which make it possible to use CNFs for applications in biomedical research. In this work, CNFs are disintegrated from poplar wood powders by chemical pretreatment combined with ultrasonication treatment, then make Indomethacin (IMC) crystal growth on the surfaces of CNFs to form CNFs/IMC composite fibers by the solvent evaporation self-assembly method. Using solvent method and freeze-drying processing to prepare cellulose nanofibers-based biological scaffolds with bovine serum albumin (BSA) nanoparticles. Change for morphology, structure of crystal, microstructure and morphology of interface and composite fibers, drug loading capacity and in vitro drug release effect are characterized and analyzed by transmission electron microscope, scanning electron microscope, optical microscope, fourier transform infrared spectroscopy, X-ray diffraction and high performance liquid chromatography. The mechanism of CNFs drug-loading and the effects of experimental factors have been explored and the influences of different preparation methods are compared and optimal one is chosen. It can be obtained the optimal biological scaffolds preparation technology via examining diameter of BSA nanoparticles, Zeta potential and microstructures of biological scaffolds. Meanwhile, we can detect the compatibility and biological toxicity of the biological scaffolds by in vitro cell culture experiments. The main work and results can be summarized as follows:(1) The mixture solvent of distilled water and absolute ethanol with different volume ratio has been used as the main solvent. CNFs/IMC mixed suspensions with different solvents ratio have been prepared with a great diversity of methods. Through the results of SEM, we can find that model drug IMC completely composite with CNFs to form CNFs/IMC composite fibers when the content of absolute ethanol up to50%. The samples which have been ultrasonication treatment are short rodlike and stiff structures, and long and soft composite fibers are obtained by ultrasonication treatment combined with homogeneous treatment, and have uniform morphology and a certain oriention.(2) CNFs/IMC composite fibers solid samples are characterized by XRD, FTIR and DSC, which indicated that the drug crystal structure from freeze-drying composite fibers is consistent with IMC raw materials with stable y-form. While for oven-dried composite fibers there are two kinds of drug crystal type, when the content of absolute ethanol in the mixed solvent is 70%and100%, the drug crystal type is mestasable a-form, for the sample which the content of absolute ethanol is50%, the drug crystal type is stable y-form.(3) The CNFs/IMC oven-dried samples have been used for in vitro drug release experiments. The drug release curves consisted of two or three distinct phases and fitted well to the first-order equations. The total release time was over1month, and the total cumulative amounts of drug release are up to80%, drug loading capacities are up to69%and the largest entrapment efficiency is97.8%.(4) BSA nanoparticles with different preparation conditions have been test and the results as follows:when the content of ethanol within the solvent over40%, BSA nanopaticles could be prepared with large particles size and out-of-shape; BSA nanoparticles could be prepared with the largest particles size with PBS solution; with the mixed solvent at the condition of deionized water and anhydrous ethanol at the volume ratio of2:1, uniform particles size and spherical BSA nanoparticles could be prepared under the effect of glutaraldehyde crosslinking(5) Microstructures of BSA-CNFs biological scaffolds with using the CNFs prepared by ultrasonication treatment are better than those which by homogeneous treatment, which have uniform structure and fibers disperse well, CNFs form porous net-work structure and BSA nanoparticles doped within it, CNFs effectively prevent BSA nanoparticles aggregation from each other, and have the effect of supporting and loading drugs at the same time.(6) L929cells were been used to study the cellular compatibility of BSA-CNFs biological scaffolds, which have no cytotoxicity and the cells grow on the scaffolds in a good condition. The trends of L929cells in BSA-CNFs nutrient solution were consistent with those who grew up in standard nutrient solution.