SEDDS facilitate cinnamaldehyde crossing the mucus barrier: The perspective of mucus and Caco-2/HT29 co-culture models

Self-emulsifying drug delivery systems (SEDDS) have potential applications in the delivery of hydrophobic components. Oral drugs are readily captured and cleared by intestinal mucus, a natural barrier that covers the mucosal epithelium and prevents the entry of foreign substances. In this study, we investigated for the first time the ability of SEDDS to deliver the lipophilic aldehyde cinnamaldehyde (CA-SEDDS) in rat mucus, mucin solution, Caco-2 and Caco-2/HT29 co-culture monolayer systems. CA-SEDDS was characterized by particle size, Zeta potential and the logD(SEDDS/release medium). The capacity of CA-SEDDS to enhance mucus permeability was investigated in rat intestinal mucus gel and mucin solution with the period of in 12 h by Transwell (R) diffusion. We evaluated the potential of CA-SEDDS delivery of CA in a co-culture system of absorptive Caco-2 and mucus secreting HT29 cells. CA-SEDDS exhibited excellent mucus permeability in mucus and mucin solutions, 5.1- and 2.8-fold higher than the free CA group, respectively. CA-SEDDS penetration increased by 2.5-fold compared with free CA when using the mucus-secreting co-culture cell model as a barrier. The relative oral bioavailability of CA-SEDDS was 242% compared to CA without formulation. These findings suggest that SEDDS exhibited good release and superior mucus permeability, displaying great potential for the future of hydrophobic oral applications.

自乳化药物递送系统（SEDDS）在疏水性成分的递送方面具有潜在应用。口服药物很容易被肠道黏液捕获和清除，肠道黏液是一种覆盖黏膜上皮并防止外来物质进入的天然屏障。在本研究中，我们首次研究了SEDDS在大鼠黏液、黏蛋白溶液、Caco - 2细胞以及Caco - 2/HT29共培养单层系统中递送亲脂性醛类肉桂醛（CA - SEDDS）的能力。通过粒径、Zeta电位以及logD（SEDDS/释放介质）对CA - SEDDS进行了表征。通过Transwell®扩散实验，在12小时内研究了CA - SEDDS在大鼠肠道黏液凝胶和黏蛋白溶液中增强黏液通透性的能力。我们评估了CA - SEDDS在吸收性Caco - 2细胞和黏液分泌性HT29细胞共培养系统中递送肉桂醛的潜力。CA - SEDDS在黏液和黏蛋白溶液中表现出优异的黏液通透性，分别比游离肉桂醛组高5.1倍和2.8倍。当使用黏液分泌共培养细胞模型作为屏障时，与游离肉桂醛相比，CA - SEDDS的穿透率提高了2.5倍。与未制剂化的肉桂醛相比，CA - SEDDS的相对口服生物利用度为242%。这些发现表明SEDDS表现出良好的释放性能和优异的黏液通透性，在未来疏水性口服应用方面显示出巨大潜力。