Deng Feiyang, Yu Chao, Zhang Hua, Dai Wenbing, He Bing, Zheng Ying, Wang Xueqing, Zhang Qiang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Curr Drug Deliv. 2016;13(1):105-10. doi: 10.2174/1567201812666150722122657.
In the previous study, we have clarified how the hydrophilic and hydrophobic structures of amphiphilic polymers impact the transport of their micelles (PEEP-PCL, PEG-PCL and PEG-DSPE micelles) in epithelial MDCK cells (Biomaterials 2013, 34: 6284-6298). In this study, we attempt to clarify the behavior of the three micelles in rats. Coumarin-6 loaded micelles were injected into different sections of intestine of rats and observed by confocal laser scanning microscope (CLSM) or orally administrated and conducted pharmacokinetic study. All of the three kinds of micelles were able to cross the intestinal epithelial cells and enter blood circulation. The PEEP-PCL micelles demonstrated the fastest distribution mainly in duodenum, while the PEGDSPE micelles showed the longest distribution with the highest proportion in ileum of the three. No significant difference was observed among the pharmacokinetic parameters of the three micelles. The results were consistent in the two analysis methods mentioned above, yet there were some differences between in vivo and in vitro results reported previously. It might be the distinction between the environments in MDCK model and intestine that led to the discrepancy. The hydrophobicity of nanoparticles could both enhance uptake and hinder the transport across the mucus. However, there was no intact mucus in MDCK model, which preferred hydrophobic nanoparticles. PEEP was the most hydrophilic material constructing the micelles in the study and its uptake would be increased in rats compared to that in MDCK model, while DSPE was more hydrophobic than the others and MDCK model would be more ideal for its uptake. Considering the inconsistency of the results in the two models, whether the methods researchers were generally using at present were reasonable needs further investigation.
在之前的研究中，我们已经阐明了两亲性聚合物的亲水和疏水结构如何影响其胶束（PEEP-PCL、PEG-PCL和PEG-DSPE胶束）在上皮MDCK细胞中的转运（《生物材料》，2013年，34卷：6284 - 6298页）。在本研究中，我们试图阐明这三种胶束在大鼠体内的行为。将负载香豆素-6的胶束注射到大鼠肠道的不同部位，并用共聚焦激光扫描显微镜（CLSM）进行观察，或者口服给药并进行药代动力学研究。所有这三种胶束都能够穿过肠上皮细胞并进入血液循环。PEEP-PCL胶束在十二指肠的分布最快，而PEG-DSPE胶束在三者中在回肠的分布时间最长且比例最高。这三种胶束的药代动力学参数之间未观察到显著差异。上述两种分析方法的结果是一致的，但与之前报道的体内和体外结果存在一些差异。可能是MDCK模型和肠道环境的差异导致了这种不一致。纳米颗粒的疏水性既能增强摄取又会阻碍其穿过黏液的转运。然而，MDCK模型中没有完整的黏液，该模型更倾向于疏水性纳米颗粒。在本研究中，PEEP是构成胶束的最亲水材料，与MDCK模型相比，其胶束在大鼠体内的摄取会增加，而DSPE比其他材料更疏水，MDCK模型对其摄取来说会更理想。考虑到两种模型结果的不一致性，目前研究人员普遍使用的方法是否合理需要进一步研究。
