Study On Membrane Emulsification Internal Gelation Process And Properties Of Calcium Alginate Gel Beads

The research and development of stable, efficient and safe drug delivery system for biopharmaceuticals have been promoted by the contradiction between clinical demands and relative hysteretic preparation level. Alginate/chitosan microcapsules (ACA microcapsules) have been proven to be potential drug delivery carrier for biopharmaceuticals, due to material characteristics (biocompatibility, biodegradability and biadhesiveness) and mild reaction characteristics. As potential mass production technique of calcium alginate gel beads and ACA microcapsules, there still exist some problems in emulsification-internal gelation. The big shearing force of emulsification process makes against the maintenance of biological material activity, and the size distribution of beads is not uniform; there are lack of the illustrative and quantitative understanding to real structure of beads, and the process mechanism is not investigated though it is important to know and interpret the structure, properties and the relationship between them. Aiming at the problem above, membrane emulsification combined with internal gelation technology was developed in this dissertation, and the mechanism of internal gelation process was analyzed.Furthermore, the correlation among process mechanism------structure of gel beads--properties of beads was carried out, and its effect on microcapsule membrane structure and properties was also investigated.Firstly, membrane emulsification technology was combined with internal gelation process, making use of its ability of preparing uniform emulsion or microparticles under mild conditions. The small size and narrow distribution gelbeads with smooth surface and good sphericity were successfully obtained. Then the understanding of the effect of process parameters on the bead size, distribution and morphology would be in favor of optimizing process conditions.Secondly, based on the investigation of Ca content change in gel beads and bead weight change, together with theoretical analysis, internal gelation process was thought to be a complicate reaction process, composed of 1 diffusion process and 4 reaction steps, that is,After analyzing, calculating and comparing, HAc diffusion process was determined as the control step of internal gelation.Thirdly, confocal laser scanning microscopy (CLSM) was introduced into structure characterization of calcium alginate gel beads. The illustrative, real structure and quantitative pore size of beads with over 95% water were observed for the first time. Comparing the bead structure by internal gelation and external gelation, respectively, it was also found that it was the mechanism difference of gelation that resulted in different bead structure. Furthermore, the structure difference contributed to the material diffusion difference.Fourthly, structure of ACA microcapsule membrane was observed using CLSM. It was noticed that the membrane structure was determined by bead structure, and was denser than the latter. It was shown for the first time that the membrane pores were asymmetric along Z axis instead of straight through ones. Further studies revealed that the membrane strength of microcapsules was affected by membrane structure.Finally, taking hemoglobin (Hb, Mw 64,500 Dalton) as model drug, the Hb-ACA microcapsules were prepared. The effect of membrane formation reaction conditions on drug loading, entrapment efficiency and release property were investigated, which showed sustained release behaviour to a certain extent.