Huang Jiahao, Chen Peter X, Rogers Michael A, Wettig Shawn D
School of Pharmacy, University of Waterloo, Waterloo, ON N2L3G1, Canada.
Department of Food Science, University of Guelph, Guelph, ON N1G2W1, Canada.
Pharmaceutics. 2019 Apr 2;11(4):156. doi: 10.3390/pharmaceutics11040156.
Phyto-phospholipid complexes have been developed as a common way of improving the oral bioavailability of poorly absorbable phyto-pharmaceuticals; however, the complexation with phospholipids can induce positive or negative effects on the bioaccessibility of such plant-derived active ingredients in different parts of the gastrointestinal tract (GIT). The purpose of this study was to investigate the effects of phospholipid complexation on the bioaccessibility of a rosmarinic acid-phospholipid complex (RA-PLC) using the TNO dynamic intestinal model-1 (TIM-1). Preparation of RA-PLC was confirmed using X-ray diffraction, Fourier-transform infrared spectroscopy, partition coefficient measurement, and Caco-2 monolayer permeation test. Bioaccessibility parameters in different GIT compartments were investigated. Complexation by phospholipids reduced the bioaccessibility of RA in jejunum compartment, while maintaining the ileum bioaccessibility. The overall bioaccessibility of RA-PLC was lower than the unformulated drug, suggesting that the improved oral absorption from a previous animal study could be considered as a net result of decreased bioaccessibility overwhelmed by enhanced intestinal permeability. This study provides insights into the effects of phospholipid on the bioaccessibility of hydrophilic compounds, and analyzes them based on the relationship between bioaccessibility, membrane permeability, and bioavailability. Additionally, TIM-1 shows promise in the evaluation of dosage forms containing materials with complicated effects on bioaccessibility.
植物磷脂复合物已被开发为提高难吸收植物药口服生物利用度的常用方法；然而，与磷脂的络合可能会对胃肠道（GIT）不同部位此类植物源活性成分的生物可及性产生正面或负面影响。本研究的目的是使用荷兰应用科学研究院动态肠道模型-1（TIM-1）研究磷脂络合对迷迭香酸-磷脂复合物（RA-PLC）生物可及性的影响。通过X射线衍射、傅里叶变换红外光谱、分配系数测量和Caco-2单层渗透试验确认了RA-PLC的制备。研究了不同胃肠道区域的生物可及性参数。磷脂络合降低了RA在空肠区域的生物可及性，同时保持了回肠的生物可及性。RA-PLC的总体生物可及性低于未制剂化药物，这表明先前动物研究中口服吸收的改善可被视为生物可及性降低被肠道通透性增强所抵消的净结果。本研究深入探讨了磷脂对亲水性化合物生物可及性的影响，并基于生物可及性、膜通透性和生物利用度之间的关系对其进行了分析。此外，TIM-1在评估对生物可及性有复杂影响的材料的剂型方面显示出前景。
