PMID- 32079270 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1999-4923 (Print) IS - 1999-4923 (Electronic) IS - 1999-4923 (Linking) VI - 12 IP - 2 DP - 2020 Feb 17 TI - Transport Mechanisms of Polymannuronic Acid and Polyguluronic Acid Across Caco-2 Cell Monolayers. LID - 10.3390/pharmaceutics12020167 [doi] LID - 167 AB - Detailed knowledge of the intestinal transport of polymannuronic acid (PM) and polyguluronic acid (PG) is critical for understanding their biological activities. To investigate the transport in the gastrointestinal tract, PM and PG were chemically modified with tyramine and conjugated with fluorescein isothiocyanate (FITC) to synthesize FITC-PM (F-PM) and FITC-PG (F-PG) successfully. The transport mechanisms of F-PM and F-PG across the intestinal epithelial cell monolayers (Caco-2 cell monolayers) were then investigated. The results demonstrated that the transport of F-PM and F-PG into epithelial cells was time- and energy-dependent, which was mediated by the macropinocytosis pathway and the clathrin- and caveolae (or lipid raft)-mediated endocytic pathway. The transport process of F-PM and F-PG in Caco-2 cells depended on the acidification of endosomes and involved lysosomes. Tubulin mediated the transport of F-PM, but not of F-PG. Moreover, the absorption enhancer chitosan (CS) promoted the transport of F-PM and F-PG, increasing the apparent permeability coefficient (Papp) by 1.9-fold and 2.6-fold, respectively, by reversibly opening the tight junction (TJ). In summary, this study provided a comprehensive understanding of the transport of PM and PG in the small intestinal epithelial cells, which will provide a theoretical basis for the development of PM and PG with good intestinal absorption. FAU - Wang, Yu AU - Wang Y AD - Marine College, Shandong University, Weihai, Weihai 264209, China. FAU - Bai, Xu AU - Bai X AD - Marine College, Shandong University, Weihai, Weihai 264209, China. FAU - Hu, Bo AU - Hu B AD - Marine College, Shandong University, Weihai, Weihai 264209, China. FAU - Xing, Maochen AU - Xing M AD - Marine College, Shandong University, Weihai, Weihai 264209, China. FAU - Cao, Qi AU - Cao Q AD - Marine College, Shandong University, Weihai, Weihai 264209, China. FAU - Ji, Aiguo AU - Ji A AD - Marine College, Shandong University, Weihai, Weihai 264209, China. AD - School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. FAU - Song, Shuliang AU - Song S AD - Marine College, Shandong University, Weihai, Weihai 264209, China. LA - eng GR - ZR2017MH040/Natural Science Foundation of Shandong Province/ PT - Journal Article DEP - 20200217 PL - Switzerland TA - Pharmaceutics JT - Pharmaceutics JID - 101534003 PMC - PMC7076430 OTO - NOTNLM OT - Caco-2 cell monolayers OT - polyguluronic acid OT - polymannuronic acid OT - transport mechanisms COIS- The authors declare no conflict of interest. EDAT- 2020/02/23 06:00 MHDA- 2020/02/23 06:01 PMCR- 2020/02/01 CRDT- 2020/02/22 06:00 PHST- 2020/01/23 00:00 [received] PHST- 2020/02/14 00:00 [revised] PHST- 2020/02/14 00:00 [accepted] PHST- 2020/02/22 06:00 [entrez] PHST- 2020/02/23 06:00 [pubmed] PHST- 2020/02/23 06:01 [medline] PHST- 2020/02/01 00:00 [pmc-release] AID - pharmaceutics12020167 [pii] AID - pharmaceutics-12-00167 [pii] AID - 10.3390/pharmaceutics12020167 [doi] PST - epublish SO - Pharmaceutics. 2020 Feb 17;12(2):167. doi: 10.3390/pharmaceutics12020167.