脂质体对肠道吸收补铁剂的调控作用

Iron deficiency is the most common and widespread nutrient disorder in the world, especially affecting a large number of women and children in developing countries (e.g. China), as well as the only nutrition deficiency which is still significantly prevalent in developed countries. Increasing iron supplement intake is considered as the most effective and economical strategy to combat iron deficiency. However, there are some disadvantages of the most commonly used iron supplements (for instance, ferrous sulfate), such as low bioavailable, not stable, bad tasting. In previous studies, the fact has been confirmed that iron supplements can be loaded into liposomal delivery vehicles, and the bioavailability of iron supplements could be significantly increased by encapsulating into liposomes, and iron supplement liposomes more effectively combated iron deficiency. However, the regulation of liposomes on the intestinal absorption of iron supplement is still unclear. In the program, Caco-2 cell model and in situ intestinal perfusion model will be used to investigate the regulation of liposomes on the intestinal absorption of iron supplement in vitro and in vivo. Firstly, the effects of key factors for common iron absorption (e. g. divalent metal transporter-1) on the absorption of iron supplement liposomes will be researched. Secondly, the effects of liposomal apparent parameters on intestinal absorption of iron supplement will be studied, and the characteristic of intestinal absorption bias of iron supplement liposomes will be investigated. Thirdly, the relation between liposomal apparent parameters and intestinal absorption of iron supplement liposomes will be extracted by genetic algorithm (GA). And the effect weights of liposomal apparent parameters on intestinal absorption of iron supplements will be evaluated. The control factors for intestinal absorption bias of iron supplement liposomes will be discussed. The importace of liposomal apparent parameters on regulation of liposomes will be revealed. The program is significant for clearing the internal relationship between liposomal apparent parameters and intestinal absorption of iron supplement liposomes, uncovering the regulation of liposomes on intestinal absorption of iron supplement. Iron deficiency, a worldwide malnutrition problem, is explored in the study, and the theory evidences will be provided for the application of iron supplement liposomes.

铁缺乏是一个世界性的营养不良问题，增加铁剂的摄入量是解决这一问题最经济的方法。课题组前期研究发现补铁剂脂质体比传统补铁剂在改善缺铁症方面效果更佳，但脂质体对肠道吸收补铁剂的调控作用仍不清楚。本项目拟采用Caco-2细胞模型和在体肠灌流模型，从体外和体内两方面研究肠道对补铁剂脂质体的吸收规律，探寻影响传统补铁剂吸收的关键因素对肠道吸收补铁剂脂质体的作用规律；分析表观参数对肠道吸收补铁剂脂质体的行为的影响，探讨肠道对补铁剂脂质体的吸收偏好；进一步利用遗传算法抽提表观参数与补铁剂脂质体吸收效率的关系，挖掘表观参数对肠道吸收补铁剂脂质体效率的作用权重，明确肠道偏好吸收补铁剂脂质体的受控因素，揭示表观参数对脂质体调控作用的影响本质。本研究将量化分析表观参数与吸收效率之间的内在关系，阐明脂质体对肠道吸收补铁剂的调控作用；并对改善人体铁缺乏这一世界性难题进行探索，将为补铁剂脂质体的实际应用提供理论依据。

铁缺乏是一个世界性的营养不良问题，该问题在我国也同样广泛存在。课题组前期研究发现补铁剂脂质体比传统补铁剂能够更有效地改善缺铁症，但关于传统因素和理化参数对补铁剂脂质体吸收的影响仍不清楚。项目研究主要包括：(1) 采用Caco-2细胞模型、在体肠灌流模型和外翻肠囊模型等系统研究了传统补铁剂吸收的主要影响因素对补铁剂脂质体吸收效率的影响，结果表明，在常见的铁吸收抑制剂存在时，如植酸、锌，补铁剂与补铁剂脂质体的铁的吸收效率都会下降，且随着抑制剂含量的增加，两者的铁吸收效率会进一步下降，但补铁剂脂质体铁吸收效率受到的抑制明显更轻。抗坏血酸明显促进游离补铁剂的吸收，而补铁剂脂质体的吸收却几乎不受其影响。(2) 采用Caco-2细胞模型、在体肠灌流模型等系统研究了脂质体理化参数对补铁剂脂质体吸收效率的影响，结果表明，卵磷脂-胆固醇由20:0提高到20:2时，补铁剂脂质体的吸收呈增加趋势；当两者比例由20:2提高到20:4时，其吸收则会降低。卵磷脂与吐温80由10:0提高到10:5时，补铁剂脂质体的吸收明显增加；当两者比例由10:5提高到10:20时，其吸收则降低。卵磷脂与补铁剂由10:1提高到10:2时，补铁剂脂质体的吸收增加；当两者比例由10:2提高到10:4时，其吸收则降低。其补铁剂脂质体的吸收高度依赖于粒径尺寸，随着粒径尺寸由1000 nm减小到100 nm，其吸收显著增加。(3) 采用遗传算法构建了主要表观参数与补铁剂脂质体吸收关系的数学模型。评价了各变量对补铁剂脂质体吸收影响的相对重要性，变量的重要性顺序为：吐温80>芯材>卵磷脂>胆固醇。并预测有最优吸收的补铁剂脂质体的表观参数为：卵磷脂：胆固醇：吐温80：芯材=10:1.6724:16.8764:15.9690。项目结果表明脂质体可有效地将补铁剂包封，且减小抑制剂对其吸收的影响。除了载体功能外，脂质体还可能增加补铁剂亲和性，改变细胞信号传导等。构建的数学模型可有效评估理化参数对补铁剂脂质体吸收的影响权重和预测其吸收效率。研究结果可用于指导脂质体运载补铁剂，以及为预防和治疗铁缺乏症方面提供了高效的路径。