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

• Published in: International journal of pharmaceutics 2022-02, Vol.614, p.121461-121461, Article 121461
• Main Authors: Cai, Ye, Liu, Liu, Xia, Mengqiu, Tian, Chunling, Wu, Wenqing, Dong, Baoqi, Chu, Xiaoqin
• Format: Article
• Language: English
• Subjects: Acrolein - analogs & derivatives; Animals; Caco-2 cell; Caco-2 Cells; Cinnamaldehyde; Coculture Techniques; Drug Delivery Systems; Emulsions; HT29 cell; Humans; Mucus; Pharmacokinetics; Rats; SEDDS
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.121461

[Display omitted] 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 logDSEDDS/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® 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.