海藻酸钠-壳聚糖微胶囊作为肠道内生化微反应器的研究

基因工程技术的发展使蛋白、多肽类高值生化药物的大规模生产得以实现并用于临床^1].但目前存在产物分离、纯化工艺复杂、成本高等问题.因此,研制一种无需分离纯化、低成本的肠道内生化微反应器作为基因工程药物释放系统具有实际应用意义(例如将基因工程微生物包埋在具有半透性高分子膜的微胶囊中,口服后微囊化活细胞在肠道内生长并分泌有治疗作用的基因工程药物而达到治疗目的^2]).本文以酵母菌Pichia pastoris GS115为模型菌株,以海藻酸钠-壳聚糖(A lginate-chitosan,AC)微胶囊为载体,考察了AC微囊化酵母菌在模拟胃肠液中的形态、膨胀性能、酵母菌存活率及小鼠口服后肠道黏膜粘附性能,初步证明AC微囊化基因工程酵母菌作为肠道生化微反应器是可行的.

Sodium Alginate-chitosan Microcapsules Using as Bio-microreactor in Intestinal Tract

An intestinal bio-microreactor with potential application prospect as a drug delivery system was proposed and studied. It was designed to overcome the problems such as complexity of separation and purification, and subsequent high costs, which always exist in producing genetically engineered drugs. For example, the process of separation and purification can be omitted by oral administration of genetically engineered microbes entrapped in semi-permeable membrane of microcapsules. The microencapsulated cells can live, metabolize and secrete therapeutic proteins in intestinal tract. In this paper, Pichia pastoris GS115 was selected as the model microbe, alginate-chitosan (AC) microcapsules as the carrier, and the physicochemical performance of the intestinal bio-microreactor was studied. It was found that the encapsulation efficiency of living yeast cells during the preparation of microcapsules was about 80%. It was shown that all AC microcapsules with yeast cells were kept intact in simulated gastric solution and simulated intestinal solution, and the survival of microencapsulated cells in simulated gastrointestinal solutions was 200-times higher than that of free cells, which showed that AC microcapsules can protect the activity of yeast cells. Furthermore, when being orally administered in mice, AC microcapsules could go through stomach and adhere to the surface of small intestinal mucous membrane over 12 h. Therefore, it was concluded that AC microencapsulated yeast cells could be used as intestinal bio-microreactor to secret bio-drugs in vivo directly.