食品功能因子稳态化淀粉-亲水胶体载体的构建及其机理研究

This project uses starch, a natural polymer, as study material to comprehensively investigate the correlations between starch structure and carrier characteristics as well as its releasing property with the aim to manipulate its functionality. The study is based on design, self-assembly and manipulation of starch macromolecular structure with the target of stabilization of lipid-soluble functional molecules. The project will modify the starch structure based on chain structure and its aggregation behavior; develop a starch-hydrocolloid complex carrier through complexing starch with guar gum; manipulate starch chain structure and state of aggregation at molecular level; establish the relationship between carrier hydrolysis characteristics and the roles of starch botanical sources, modification methods, the ratio of starch and hydrocolloid, and the complexation conditions; and investigate the mechanism of interactions between starch of various structures and hydrocolloids. The project will use the conjugated linoleic acid as target model and load it into the starch carrier through self-assembled interfacial reaction. The stability, in vitro and in vivo releasing property of conjugated linoleic acid and its releasing mechanism will be determined. The objective of this project is to design carrier structure using molecular dynamics techniques, explore the possible carrier solutions for significantly stabilizing the conjugated linoleic acid and increase the bioavailability and stability of lipid-soluble functional molecules.

本项目以天然高分子淀粉为研究对象，以淀粉大分子结构设计、自组装及功能化为基础，稳态化脂溶性功能因子为导向，系统研究淀粉结构与载体特性的构效关系及释放性等基础科学问题，实现该组装可控功能化。项目基于淀粉的链结构及聚集态特点，对其进行修饰，并与亲水胶体复配，构建淀粉-亲水胶体载体，从分子层面上调控淀粉链结构和聚集态，明确淀粉品种、修饰手段、复配比例和条件与载体水解特性之间的相关性，探究不同结构的淀粉与亲水胶体在复配过程中的作用机制；以共轭亚油酸为靶向目标模型，采用自组装界面反应将其载入至载体，研究其稳定性，体内外实验建立共轭亚油酸的释放动力学模型，确定释放机制；通过分子动力学技术设计载体结构，探索能明显改变载体稳态化共轭亚油酸的调控策略，提高脂溶性功能因子的生物利用度和稳定性。

本项目以天然高分子淀粉为研究对象，稳态化脂溶性功能因子为导向，系统研究淀粉结构与载体特性的构效关系及释放性等基础科学问题。项目利用辛烯基琥珀酸淀粉酯（OSA淀粉）和黄原胶复配作为载体包埋保护共轭亚油酸（CLA），减少其在胃内的损失，提高其在人体肠道中的利用率。研究发现CLA微胶囊的包埋率均高于97%，微胶囊在模拟胃液中CLA的累积释放率在3.6%~6.1%之间；在模拟小肠液中，CLA的释放率在12.1%~50.1%之间，采取荧光标记示踪法间接测定CLA在动物消化道内转运情况，证明CLA在大鼠胃中释放极少，在小肠释放大部分CLA，表现了较好的缓释性能。研究了脱支淀粉和黄原胶复配载体结构性质以及茶多酚微胶囊缓释效果，大鼠体内的降血脂动物实验验证了茶多酚微胶囊比直接灌胃茶多酚粉末具有更明显的降血脂效果。探究了复配载体的结构性质与微胶囊缓释效果之间的关系。此结果表明连续、致密多孔、交联缠绕的网络结构更利于阻碍茶多酚从载体中释放；高粘性和抗剪切性的复配载体更利于阻碍茶多酚的扩散，实现茶多酚的缓释。探究脱支淀粉基质片剂缓释性能和释药机制，研究发现脱支淀粉基质片剂体外释药过程为II相不规则转运机制。糖尿病大鼠口服实验发现表面裹附一层壳聚糖的三元纳米复合物的药理生物利用度和相对生物利用度分别提高至14.12%和15.19%，降血糖作用更为明显。研究纳米复合物的吸收转运行为，表明纳米复合物可以促进Caco-2 细胞对胰岛素的摄取量。急性毒性和亚急性毒性实验表明纳米复合物具有良好的生物相容性。此外，以人体消化道内环境pH值的差异为出发点，构建一种pH敏感型淀粉基载体；实现其在小肠上端的pH敏感型释放，体现在从模拟胃液转移至模拟肠液后的前30 min内释放率高达51.01%；释放动力学方程表明载体在模拟胃液中以Fick扩散、Fick扩散-载体降解溶蚀作用为主；在模拟肠液中以载体降解溶蚀为主。采用荧光标记示踪法观察并测定了维生素E在大鼠胃肠道中的转运及释放情况，结果表明该运载体系可以有效地保护维生素E至小肠释放、吸收，从而提高其生物利用度。