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Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine

We attempted to design irbesartan nanocrystalline (IRB-NC) suspensions by the bead mill method, and we evaluated the bioavailability (BA) in the oral administration of the nanocrystalline drug. The mean particle size of the IRB-NC suspensions was approximately 140 nm, and the crystalline structure o...

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Autores principales: Deguchi, Saori, Ogata, Fumihiko, Watanabe, Masaki, Otake, Hiroko, Yamamoto, Naoki, Kawasaki, Naohito, Nagai, Noriaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472685/
https://www.ncbi.nlm.nih.gov/pubmed/34575479
http://dx.doi.org/10.3390/pharmaceutics13091404
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author Deguchi, Saori
Ogata, Fumihiko
Watanabe, Masaki
Otake, Hiroko
Yamamoto, Naoki
Kawasaki, Naohito
Nagai, Noriaki
author_facet Deguchi, Saori
Ogata, Fumihiko
Watanabe, Masaki
Otake, Hiroko
Yamamoto, Naoki
Kawasaki, Naohito
Nagai, Noriaki
author_sort Deguchi, Saori
collection PubMed
description We attempted to design irbesartan nanocrystalline (IRB-NC) suspensions by the bead mill method, and we evaluated the bioavailability (BA) in the oral administration of the nanocrystalline drug. The mean particle size of the IRB-NC suspensions was approximately 140 nm, and the crystalline structure of irbesartan in these suspensions was different using the bead mill method. The aggregation and degradation of irbesartan were not observed for one month, and the solubility increased. Moreover, the inclusion complex formation of IRB-NC suspensions with 2-hydroxypropyl-β-cyclodextrin was higher than that in traditional IRB powder (IRB-P). In addition, the intestinal absorption of IRB-NC suspensions was higher than that of IRB-P suspensions, and the reducing effect on blood pressure in spontaneously hypertensive SHR-SP rats orally administered IRB-NC suspensions was significantly higher than in those administered IRB-P suspensions. On the other hand, the intestinal penetration of IRB-NC suspensions was attenuated by the inhibitors of clathrin-dependent endocytosis (CME). In conclusion, we improved the low oral BA of irbesartan by preparing IRB-NC suspensions and showed that both the solubility and CME are related to the enhanced intestinal absorption of IRB-NC suspensions, resulting in an increase in their antihypertensive effect. These findings provide significant information for the development of oral nanomedicines.
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spelling pubmed-84726852021-09-28 Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine Deguchi, Saori Ogata, Fumihiko Watanabe, Masaki Otake, Hiroko Yamamoto, Naoki Kawasaki, Naohito Nagai, Noriaki Pharmaceutics Article We attempted to design irbesartan nanocrystalline (IRB-NC) suspensions by the bead mill method, and we evaluated the bioavailability (BA) in the oral administration of the nanocrystalline drug. The mean particle size of the IRB-NC suspensions was approximately 140 nm, and the crystalline structure of irbesartan in these suspensions was different using the bead mill method. The aggregation and degradation of irbesartan were not observed for one month, and the solubility increased. Moreover, the inclusion complex formation of IRB-NC suspensions with 2-hydroxypropyl-β-cyclodextrin was higher than that in traditional IRB powder (IRB-P). In addition, the intestinal absorption of IRB-NC suspensions was higher than that of IRB-P suspensions, and the reducing effect on blood pressure in spontaneously hypertensive SHR-SP rats orally administered IRB-NC suspensions was significantly higher than in those administered IRB-P suspensions. On the other hand, the intestinal penetration of IRB-NC suspensions was attenuated by the inhibitors of clathrin-dependent endocytosis (CME). In conclusion, we improved the low oral BA of irbesartan by preparing IRB-NC suspensions and showed that both the solubility and CME are related to the enhanced intestinal absorption of IRB-NC suspensions, resulting in an increase in their antihypertensive effect. These findings provide significant information for the development of oral nanomedicines. MDPI 2021-09-03 /pmc/articles/PMC8472685/ /pubmed/34575479 http://dx.doi.org/10.3390/pharmaceutics13091404 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Deguchi, Saori
Ogata, Fumihiko
Watanabe, Masaki
Otake, Hiroko
Yamamoto, Naoki
Kawasaki, Naohito
Nagai, Noriaki
Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine
title Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine
title_full Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine
title_fullStr Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine
title_full_unstemmed Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine
title_short Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine
title_sort nanocrystalline suspensions of irbesartan enhance oral bioavailability by improving drug solubility and leading endocytosis uptake into the intestine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472685/
https://www.ncbi.nlm.nih.gov/pubmed/34575479
http://dx.doi.org/10.3390/pharmaceutics13091404
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