Cargando…
Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization
Koumine (KME) is an active alkaloid extracted from Gelsemium elegans, and its diverse bioactivities have been studied for decades. However, KME exhibits poor solubility and low oral bioavailability, which hampers its potential therapeutic exploitation. This work aimed to develop optimized inclusion...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592623/ https://www.ncbi.nlm.nih.gov/pubmed/34763595 http://dx.doi.org/10.1080/10717544.2021.1998248 |
_version_ | 1784599502804484096 |
---|---|
author | Hu, Qing Fu, Xiaoling Su, Yanping Wang, Yanfang Gao, Sihuan Wang, Xiaoqin Xu, Ying Yu, Changxi |
author_facet | Hu, Qing Fu, Xiaoling Su, Yanping Wang, Yanfang Gao, Sihuan Wang, Xiaoqin Xu, Ying Yu, Changxi |
author_sort | Hu, Qing |
collection | PubMed |
description | Koumine (KME) is an active alkaloid extracted from Gelsemium elegans, and its diverse bioactivities have been studied for decades. However, KME exhibits poor solubility and low oral bioavailability, which hampers its potential therapeutic exploitation. This work aimed to develop optimized inclusion complexes to improve the bioavailability of KME. The KME/hydroxypropyl-β-cyclodextrin (KME/HP-β-CD) inclusion complexes were prepared by the solvent evaporation method and later optimized using the Box-Behnken design. The optimal KME/HP-β-CD was characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, differential scanning calorimetry, and nuclear magnetic resonance spectroscopy. The physicochemical characterization results revealed that the crystalline state of KME was transformed into an amorphous form, forming KME/HP-β-CD inclusion complexes. Compared with KME, the solubility and in vitro release rate of KME/HP-β-CD was significantly enhanced by 52.34- and 1.3-fold, respectively. Further research was performed to investigate the intestinal absorption characteristics and in vivo bioavailability in rats. The optimal KME/HP-β-CD showed enhanced absorptive permeability and relative bioavailability increased more than two-fold compared to that of raw KME. These results indicate that the optimal KME/HP-β-CD can be used as an effective drug carrier to improve the solubility, intestinal absorption, and bioavailability of KME. |
format | Online Article Text |
id | pubmed-8592623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-85926232021-11-16 Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization Hu, Qing Fu, Xiaoling Su, Yanping Wang, Yanfang Gao, Sihuan Wang, Xiaoqin Xu, Ying Yu, Changxi Drug Deliv Research Article Koumine (KME) is an active alkaloid extracted from Gelsemium elegans, and its diverse bioactivities have been studied for decades. However, KME exhibits poor solubility and low oral bioavailability, which hampers its potential therapeutic exploitation. This work aimed to develop optimized inclusion complexes to improve the bioavailability of KME. The KME/hydroxypropyl-β-cyclodextrin (KME/HP-β-CD) inclusion complexes were prepared by the solvent evaporation method and later optimized using the Box-Behnken design. The optimal KME/HP-β-CD was characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, differential scanning calorimetry, and nuclear magnetic resonance spectroscopy. The physicochemical characterization results revealed that the crystalline state of KME was transformed into an amorphous form, forming KME/HP-β-CD inclusion complexes. Compared with KME, the solubility and in vitro release rate of KME/HP-β-CD was significantly enhanced by 52.34- and 1.3-fold, respectively. Further research was performed to investigate the intestinal absorption characteristics and in vivo bioavailability in rats. The optimal KME/HP-β-CD showed enhanced absorptive permeability and relative bioavailability increased more than two-fold compared to that of raw KME. These results indicate that the optimal KME/HP-β-CD can be used as an effective drug carrier to improve the solubility, intestinal absorption, and bioavailability of KME. Taylor & Francis 2021-11-12 /pmc/articles/PMC8592623/ /pubmed/34763595 http://dx.doi.org/10.1080/10717544.2021.1998248 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Hu, Qing Fu, Xiaoling Su, Yanping Wang, Yanfang Gao, Sihuan Wang, Xiaoqin Xu, Ying Yu, Changxi Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization |
title | Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization |
title_full | Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization |
title_fullStr | Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization |
title_full_unstemmed | Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization |
title_short | Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization |
title_sort | enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592623/ https://www.ncbi.nlm.nih.gov/pubmed/34763595 http://dx.doi.org/10.1080/10717544.2021.1998248 |
work_keys_str_mv | AT huqing enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization AT fuxiaoling enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization AT suyanping enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization AT wangyanfang enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization AT gaosihuan enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization AT wangxiaoqin enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization AT xuying enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization AT yuchangxi enhancedoralbioavailabilityofkouminebycomplexationwithhydroxypropylbcyclodextrinpreparationoptimizationexvivoandinvivocharacterization |