水力空化强化壳聚糖微球的制备及其对颗粒特征的影响研究

Preparation of chitosan microsphere is one of research hotspots in high-value processing and utilization of chitosan resource. There exist long emulsification time in mixture of oil and water, difficulty in homogeneity of oil and water, low mass transfer rate in reaction and out of control in size distribution of microsphere for preparation of chitosan microsphere by using conventional methods at present. In this research, the effect of hydrodynamic cavitation will be used for intensification of both of the key points that are the emulsification process and the cross-linking reaction in the emulsion cross-linking method, which is the most widely used for the preparation of chitosan microsphere in conventional methods. The effect of molecular weight of chitosan, rheological properties of chitosan solution, emulsification condition, types and structure parameters of cavitation component, and multi-stage hydrodynamic cavitation on the particle characteristics of chitosan microsphere will be systematically studied. Both the hydrodynamic cavitation bubble dynamics and the hydrodynamic cavitation field in the heterogeneous emulsion of oil and aqueous chitosan solution will be studied by using computer simulations, which can provide the basis for the choice of cavitation component and the structure optimization of cavitation component. By combining with the experimental test and calculated results of cavitation number, the influence mechanism of the micro-mixing scale of emulsification process which is intensified by hydrodynamic cavitation on particle characteristics will be studied by using numerical simulation, which can provide theoretical basis for the intensification of preparation of chitosan microsphere with emulsion cross-linking method by using hydrodynamic cavitation. The studied results will provide important significance for promoting the research of hydrodynamic cavitation on the intensification of preparation of chitosan microsphere and polysaccharide microsphere.

壳聚糖微球制备是壳聚糖资源高值化加工与利用研究的热点之一。目前壳聚糖微球常规法制备大多存在油-水混合乳化时间长、油-水混合均质困难、反应传质速率慢、微球粒径分布不可控等问题，而现有技术均未能有效解决或是尚处于理论研究阶段。本项目以常规法中最广泛使用的乳化交联法为研究对象，采用水力空化效应强化该法中的乳化过程和交联反应这两个关键点，系统研究壳聚糖分子量、壳聚糖溶液流变性质、乳化条件、空化元件类型及结构参数、多级水力空化等对壳聚糖微球颗粒特征的影响规律；并对非均相油-壳聚糖水溶液乳化体系的空泡动力学、空化流场进行计算机模拟，为空化元件选择及结构优化提供依据；同时结合实验测定和计算空化数，通过数值模拟研究水力空化强化乳化过程的非均相微观混合尺度对壳聚糖微球颗粒特征的影响机制，为水力空化强化乳化交联法制备壳聚糖微球提供理论依据。研究结果对水力空化强化壳聚糖微球乃至多糖微球的制备具有重要价值。

壳聚糖(CS)微球制备是壳聚糖资源高值化利用的研究热点，且水力空化（HC）强化微粒制备研究仍处于理论空白。本项目系统研究CS分子量、流变性质、乳化条件、单级空化和多级空化等对微粒特征的影响规律，并探讨不同空化方式对非均相微观混合尺度的作用规律及其对颗粒大小的影响机制。研究结果表明：.HC制出了粒度小、分布窄，且尺寸在230~1500nm范围可控的纳米级微粒。与传统石蜡油相比，棕榈油更适合作为连续相；戊二醛以W/O乳液的添加方式为宜；增大CS分子量，微粒的粒度增大，分布变宽，但产率提高。微粒成球性、产率和颗粒形貌对溶解CS的溶剂性质、CS溶液流变学性质存在强依赖性；HLB≥8.3或油/水比≥10:1，微粒表面越粗糙，团聚加剧。宜选用开孔率小，比周长大的孔板；相比戊二醛，京尼平交联制得的微粒成球性更好，产率更高。制备效果比较表明：三级空化>二级空化>单级空化。微粒在模拟胃液缓冲溶液中释放最快，小肠环境次之，而在大肠中的释放最慢，且在100h内，5-Fu药物累计释放率可达92.3%。. 增大CS分子量、脱乙酰度，水相和油相间的非均相微观混合尺度变弱；提高内水相含量（φw），乳液粘度增大，且其表现出对φw强依赖性；Span-80用量>8%不利于形成窄分布的纳米乳液，且减弱了非均相微观混合尺度；增大入口压力，或降低空化数，非均相的微观混合尺度提高。数值模拟表明：壳聚糖W/O型乳液粘度与其粒径满足单调递减的幂函数关系；聚结是造成壳聚糖W/O型乳液失稳的主要机制；乳液的不稳定性可诱导交联制得微粒粒度增大、分布变宽，且粘连性加剧；微粒大小与壳聚糖W/O型乳状液非均相微观混合尺度呈正相关。. 以上研究表明：HC可有效强化乳化交联过程获得粒度小、分布窄、尺寸可控，且能负载活性药物的纳米级CS微粒。