Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine

As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated tha...

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Autores principales:	Hisanao Kishimoto, Kaori Miyazaki, Hiroshi Tedzuka, Ryosuke Ozawa, Hanai Kobayashi, Yoshiyuki Shirasaka, Katsuhisa Inoue
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	sodium nitroprusside absorption enhancer mucus layer passive diffusion lipophilic drug Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/66cbc97d8737472fbb8f67ae55149a11
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spelling	oai:doaj.org-article:66cbc97d8737472fbb8f67ae55149a112021-11-11T18:25:11ZUtilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine10.3390/molecules262163961420-3049https://doaj.org/article/66cbc97d8737472fbb8f67ae55149a112021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6396https://doaj.org/toc/1420-3049As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a vital signaling molecule that plays an important role in various physiological systems, affects intestinal drug absorption. However, NO and its oxidants are directly toxic to the gastrointestinal tract, thereby limiting their potential clinical application as absorption enhancers. In this study, we show that sodium nitroprusside (SNP), an FDA-approved vasodilator, enhances the intestinal absorption of lipophilic drugs in the proximal parts of the small intestine in rats. The SNP pretreatment of the rat gastrointestinal sacs significantly increased griseofulvin and flurbiprofen permeation in the duodenum and jejunum but not in the ileum and colon. These SNP-related enhancement effects were attenuated by the co-pretreatment with dithiothreitol or c-PTIO, an NO scavenger. The permeation-enhancing effects were not observed in the case of antipyrine, theophylline, and propranolol in the duodenum and jejunum. Furthermore, the SNP treatment significantly increased acidic glycoprotein release from the mucosal layers specifically in the duodenum and jejunum but not in the ileum and colon. These results suggest that SNP increases lipophilic drug membrane permeability specifically in the proximal region of the small intestine through disruption of the mucosal layer.Hisanao KishimotoKaori MiyazakiHiroshi TedzukaRyosuke OzawaHanai KobayashiYoshiyuki ShirasakaKatsuhisa InoueMDPI AGarticlesodium nitroprussideabsorption enhancermucus layerpassive diffusionlipophilic drugOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6396, p 6396 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sodium nitroprusside absorption enhancer mucus layer passive diffusion lipophilic drug Organic chemistry QD241-441
spellingShingle	sodium nitroprusside absorption enhancer mucus layer passive diffusion lipophilic drug Organic chemistry QD241-441 Hisanao Kishimoto Kaori Miyazaki Hiroshi Tedzuka Ryosuke Ozawa Hanai Kobayashi Yoshiyuki Shirasaka Katsuhisa Inoue Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine
description	As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a vital signaling molecule that plays an important role in various physiological systems, affects intestinal drug absorption. However, NO and its oxidants are directly toxic to the gastrointestinal tract, thereby limiting their potential clinical application as absorption enhancers. In this study, we show that sodium nitroprusside (SNP), an FDA-approved vasodilator, enhances the intestinal absorption of lipophilic drugs in the proximal parts of the small intestine in rats. The SNP pretreatment of the rat gastrointestinal sacs significantly increased griseofulvin and flurbiprofen permeation in the duodenum and jejunum but not in the ileum and colon. These SNP-related enhancement effects were attenuated by the co-pretreatment with dithiothreitol or c-PTIO, an NO scavenger. The permeation-enhancing effects were not observed in the case of antipyrine, theophylline, and propranolol in the duodenum and jejunum. Furthermore, the SNP treatment significantly increased acidic glycoprotein release from the mucosal layers specifically in the duodenum and jejunum but not in the ileum and colon. These results suggest that SNP increases lipophilic drug membrane permeability specifically in the proximal region of the small intestine through disruption of the mucosal layer.
format	article
author	Hisanao Kishimoto Kaori Miyazaki Hiroshi Tedzuka Ryosuke Ozawa Hanai Kobayashi Yoshiyuki Shirasaka Katsuhisa Inoue
author_facet	Hisanao Kishimoto Kaori Miyazaki Hiroshi Tedzuka Ryosuke Ozawa Hanai Kobayashi Yoshiyuki Shirasaka Katsuhisa Inoue
author_sort	Hisanao Kishimoto
title	Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine
title_short	Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine
title_full	Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine
title_fullStr	Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine
title_full_unstemmed	Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine
title_sort	utilization of sodium nitroprusside as an intestinal permeation enhancer for lipophilic drug absorption improvement in the rat proximal intestine
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/66cbc97d8737472fbb8f67ae55149a11
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Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine

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