Enhancing effect of borneol and muscone on geniposide transport across the human nasal epithelial cell monolayer

• Published in: PloS one Vol. 9; no. 7; p. e101414
• Main Authors: Chen, Zhenzhen, Gong, Xin, Lu, Yang, Du, Shouying, Yang, Zhihui, Bai, Jie, Li, Pengyue, Wu, Huichao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.07.2014; Public Library of Science (PLoS)
• Subjects: Actins - metabolism; Biological Transport - drug effects; Biology and Life Sciences; Bornanes - toxicity; Borneol; Brain; Cell Membrane Permeability - drug effects; Cell Survival - drug effects; Cells, Cultured; Cerebrovascular diseases; Chromatography, High Pressure Liquid; Cycloparaffins - toxicity; Cytotoxicity; Dismantling; Drug delivery systems; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Fluidity; Fluorescence; Fluorescence recovery after photobleaching; Humans; Inflammation; Integrity; Intranasal administration; Iridoids - analysis; Iridoids - metabolism; Ischemia; Medical treatment; Medicine and Health Sciences; Membrane fluidity; Microscopy, Fluorescence; Monolayers; Monomolecular films; Nasal Mucosa - cytology; Nose; Pharmaceuticals; Photobleaching; Studies; Substrates; Toxicity; Transport; Vascular diseases; Viscosity; Beijing China; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101414

Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases.