https://scholars.lib.ntu.edu.tw/handle/123456789/573151
標題: | Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide | 作者: | Yen C.-C Chen Y.-C Wu M.-T CHIA-CHI WANG Wu Y.-T. |
關鍵字: | andrographolide; cremophor; fisetin; indometacin; water; alpha tocopherol; andrographolide; diterpene; indometacin; nanomaterial; nanoparticle; nonsteroid antiinflammatory agent; animal experiment; animal model; animal tissue; antiinflammatory activity; area under the curve; Article; chemical composition; clinical effectiveness; concentration response; controlled study; drug absorption; drug bioavailability; drug blood level; drug formulation; drug solubility; drug structure; high performance liquid chromatography; histopathology; in vivo study; inflammatory bowel disease; male; maximum concentration; membrane permeability; nanoemulsion; nonhuman; particle size; physical chemistry; physical parameters; rat; transmission electron microscopy; viscosity; administration and dosage; animal; bioavailability; C57BL mouse; chemically induced; chemistry; emulsion; enteritis; oral drug administration; permeability; solubility; Sprague Dawley rat; Administration, Oral; alpha-Tocopherol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Diterpenes; Emulsions; Enteritis; Indomethacin; Male; Mice, Inbred C57BL; Nanoparticles; Nanostructures; Permeability; Rats, Sprague-Dawley; Solubility; Viscosity; Water | 公開日期: | 2018 | 卷: | 13 | 起(迄)頁: | 669-680 | 來源出版物: | International Journal of Nanomedicine | 摘要: | Background: Andrographolide (AG), a compound with low water solubility, possesses various pharmacological activities, particularly anti-inflammatory activity. However, its low oral bioavailability is a major obstacle to its potential use. This study developed and optimized an AG-loaded nanoemulsion (AG-NE) formulation to improve AG oral bioavailability and its protective effects against inflammatory bowel disease. Methods: A high-pressure homogenization technique was used to prepare the AG-NE and solubility, viscosity, and droplet size tests were conducted to develop the optimized AG-NE composed of α-tocopherol, ethanol, Cremophor EL, and water. The permeability was assessed using everted rat gut sac method and in vivo absorption and anti-inflammatory effect in rats was also evaluated. The plasma concentration of AG was determined using our validated high performance liquid chromatography method, which was used to generate a linear calibration curve over the concentration range of 0.1-25 μg/mL in rat plasma (R2.0.999). Results: The optimized AG-NE had a droplet size of 122±11 nm confirmed using transmission electron microscopy and a viscosity of 28 centipoise (cps). It was stable at 4 and 25°C for 90 days. An ex vitro intestinal permeability study indicated that the jejunum was the optimal site for AG absorption from the optimized AG-NE, which was 8.21 and 1.40 times higher than that from an AG suspension and AG ethanol solution, respectively. The pharmacokinetic results indicate that the absorption of AG from AG-NE was significantly enhanced in comparison with that from the AG suspension, with a relative bioavailability of 594.3%. Moreover, the ulcer index and histological damage score of mice with indomethacin-induced intestinal lesions were significantly reduced by AG-NE pretreatment. Conclusion: We conclude that the developed AG-NE not only enhanced the oral bioavailability of AG in this study but may also prove to be an effective formulation of AG for preventing gastrointestinal inflammatory disorders. ? 2018 Yen et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041537033&doi=10.2147%2fIJN.S154824&partnerID=40&md5=8adab0e36aaf55015038c3ef16574d4f https://scholars.lib.ntu.edu.tw/handle/123456789/573151 |
ISSN: | 11769114 | DOI: | 10.2147/IJN.S154824 |
顯示於: | 獸醫學系 |
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