Preoaration Of Alginate Microspheres With X-ray Visualization And Drug Loading Properties By Membrane Emulsification

The polymeric microsphere has a bright future in biomedical applications. It can be used as a drug carrier, embolization material, microcapsule for cell encapsulation, etc. The polymeric microsphere can be produced by many methods, in which the membrane emulsification is an easy and effective way to prepare mono-dispersed emulsion and microspheres. Sodium alginate, a natural polymer, is widely applied in biomedical fields for its advantages of abundant resource, cheap price and good biocompatibility. In this thesis, the membrane emulsification was utilized to prepare narrow-dispersed alginate microspheres and alginate/BaSO4hybrid microspheres. Drug loading capacity was greatly enhanced after NaCl treatment of the microspheres. The release behavior and the effect on blood coagulation of alginate microspheres were investigated. X-ray visualization of alginate/BaSO4hybrid microsphere was characterized.Firstly, narrow-dispersed calcium alginate microspheres were prepared by a membrane emulsification-gelation method. The microspheres were treated with NaCl solutions of different concentrations to control the amount of free carboxylate groups. The quantity of calcium and sodium ions in the microspheres was measured by atomic absorption spectrometry and the change of functional groups was determined by Fourier transform infrared spectroscopy. During the treatment process calcium ions in the microspheres were replaced by sodium ions and the carboxylate groups were converted from a chelate to a free state. As doxorubicin hydrochloride was positive in water while alginate was negative, it was loaded into the alginate microspheres via electrostatic interaction. The loading capacity of microspheres was enhanced greatly after treatment with NaCl solution. When the microspheres were treated with1.8%NaCl solution, the drug content increased remarkably to1310μg/mg, which was nearly10times the amount of the untreated ones. The release behavior of the drug-loaded microspheres was pH-sensitive, i.e. slower at pH7.4but faster at pH5.5. The drug loaded in microspheres could be extended to other electropositive substances such as methylene blue. Secondly, large-sized calcium alginate/BaSO4hybrid microspheres, which could be used as an embolization material, were successfully prepared via the membrane emulsification method. Dextran sulfate and chitosan were coated on the surface of alginate/BaSO4hybrid microspheres via layer-by-layer assembly in order to prevent alginate and barium sulfate leaking from the microspheres after salt treatment. The result showed that after salt treatment the weight loss of microspheres coated with the multilayers was distinctly reduced compared to the microspheres without coating, while the percentage of barium sulfate in microspheres remained almost unchanged. The drug loading capacity of alginate/BaSO4hybrid microspheres was also remarkably enhanced after salt treatment. X-ray image was taken to show good X-ray visualization of alginate/BaSO4hybrid microspheres.Finally, protein adsorption and effect on blood coagulation of alginate microspheres were investigated. After salt treatment, the amount of fibrinogen adsorbed on the microspheres was reduced and whole blood coagulation time was prolonged. Doxorubicin loaded microspheres had longer coagulation time than the blank ones too.