淀粉与磷脂复合载体的诱导组装及其靶向控释递送特性

Focused on the control of the changing and response of the molecular interaction under the digestive tract environment and micro environment of cells, the key essential scientific problems on the design of starch-phospholipid complex carrier materials and the targeting controlled release delivery system which can stimulate the colonic epithelium enteroendocrine L cells to secrete the glucagon-like peptide-1 (GLP-1) will be investigated. The phospholipids are selected as molecular chaperone to induce the starch assembly. By controlling the molecular interaction between the phospholipid and starch, the starch molecular size and chain length, branch structure and the charged groups of starch molecules, the interactions among the starch and phospholipid molecules, starch/phospholipid complex and bioactive protein will be regulated and the starch-based supramolecular colloidal particles will be designed. The hydrophilic /hydrophobic property, pH-responsive, digestion resistance and stimulating endogenous GLP-1 secretion by L cells of the starch/phospholipid complex carriers and the related starch-based supramolecular colloidal particles will be deeply studied. Furthermore, the changing of the molecular interaction such as the complex, assembly, aggregation and disassemble behavior among the starch, phospholipid and bioactive protein molecules under the digestive tract environment and micro environment of cells will be revealed. These studies will offer the rational method and mechanism of controlling the complex of starch and phospholipid, the microstructure of starch-based supramolecular colloidal particles and the properties of targeting controlled release and stimulating endogenous GLP-1 secretion. The results will facilitate to the bioavailability of the bioactive proteins.

从控制分子间相互作用在消化道环境和细胞微环境下的动态变化及响应性的新颖角度，开展淀粉-磷脂复合载体及其控释递送系统构建的基础科学研究。以磷脂为分子伴侣，通过控制淀粉分子链大小、支叉结构和带电基团及其与磷脂分子的复合方式，诱导淀粉与磷脂分子间、淀粉-磷脂复合载体与蛋白营养组分间的分子相互作用，构建淀粉基超分子胶粒控释递送系统。系统考察淀粉-磷脂复合载体及淀粉基超分子胶粒的亲疏水性能、pH响应性、抗消化性能和触发结肠上皮内分泌L细胞分泌胰高血糖素样肽-1（GLP-1）的特性，揭示淀粉与磷脂、淀粉-磷脂复合载体与蛋白营养组分之间的分子内和分子间复合、组装、聚集、解离等分子相互作用行为在消化道环境和细胞微环境下的动态演变，获得合理调控淀粉与磷脂复合、淀粉基超分子胶粒结构与靶向控释递送、L细胞分泌GLP-1特性的有效方法及机制，为提高蛋白类营养组分的生物利用有效性提供理论依据。

随着人民生活水平的提高和慢性疾病谱的演变，糖尿病及其并发症已成为危害人类健康水平的世界性公共健康问题。分布在结肠的L细胞在食品功能因子刺激下分泌胰岛血糖素样肽-1（GLP-1）并通过肠-脑轴系统调控胰岛素分泌从而实现机体血糖的控制。因此，制备安全且能将功能因子靶向递送至结肠刺激L细胞分泌GLP-1的控释系统已成为当今食品科学领域所面临亟待解决的关键基础科学问题之一。.本项目从分子及分子聚集体水平上调控淀粉、磷脂与β-乳球蛋白分子间相互作用并改变磷脂分子伴侣在淀粉螺旋空腔内外的分布状态，设计克服人体消化道多重屏障的淀粉与磷脂结肠靶向递送系统。采用生物酶脱支、辛烯基琥珀酸酯化、羧甲基醚化及其与磷脂等脂质复合等方法，调节淀粉与磷脂复合载体的多尺度结构、消化性能、带电特征、亲疏水性及结肠和L细胞靶向性能，诱导淀粉与磷脂分子间、淀粉-磷脂复合载体与蛋白营养组分间的分子相互作用，赋予淀粉与磷脂复合载体材料与蛋白功能因子有效封装、结肠与L细胞靶向识别和控制释放的功能，设计出了优良的淀粉与磷脂复合载体材料及其超分子胶粒控释递送系统。该项目为实现食品功能因子靶向控释和刺激L细胞分泌GLP-1提供了新途径。.通过项目的实施，获得了靶向结肠L细胞的OSA淀粉与磷脂复合载体材料，形成了合理调控淀粉与磷脂复合、淀粉基超分子胶粒结构与靶向控释递送、L细胞分泌GLP-1特性的有效方法，建立了OSA淀粉与磷脂复合基载体材料分子结构、淀粉基超分子胶粒结构和靶向控释性能、L细胞分泌GLP-1性能间的关系，获得了调控L细胞分泌GLP-1的结肠靶向控释递送系统。研究成果为营养健康食品创制及功能因子靶向控释调控肠道激素分泌，从而调节机体血糖水平提供了基础数据与理论指导，对延伸淀粉深加工产业链，促进健康食品科学和淀粉科学的发展都具有十分重要的意义。