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Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect

Intraperitoneal injection of dihydromyricetin (DMY) has shown promising potential in the treatment of alcoholism. However, its therapeutic effect is limited due to its low solubility, poor stability, and high gut-liver first-pass metabolism, resulting in very low oral bioavailability. In this study,...

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Autores principales: Dong, Jianxia, Wang, Shu, Mao, Jiamin, Wang, Zhidan, Zhao, Shiying, Ren, Qiao, Kang, Jialing, Ye, Jing, Xu, Xiaohong, Zhu, Yujin, Zhang, Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535266/
https://www.ncbi.nlm.nih.gov/pubmed/37765265
http://dx.doi.org/10.3390/pharmaceutics15092296
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author Dong, Jianxia
Wang, Shu
Mao, Jiamin
Wang, Zhidan
Zhao, Shiying
Ren, Qiao
Kang, Jialing
Ye, Jing
Xu, Xiaohong
Zhu, Yujin
Zhang, Quan
author_facet Dong, Jianxia
Wang, Shu
Mao, Jiamin
Wang, Zhidan
Zhao, Shiying
Ren, Qiao
Kang, Jialing
Ye, Jing
Xu, Xiaohong
Zhu, Yujin
Zhang, Quan
author_sort Dong, Jianxia
collection PubMed
description Intraperitoneal injection of dihydromyricetin (DMY) has shown promising potential in the treatment of alcoholism. However, its therapeutic effect is limited due to its low solubility, poor stability, and high gut-liver first-pass metabolism, resulting in very low oral bioavailability. In this study, we developed a DMY-loaded self-emulsifying drug delivery system (DMY-SEDDS) to enhance the oral bioavailability and anti-alcoholism effect of DMY. DMY-SEDDS improved the oral absorption of DMY by facilitating lymphatic transport. The area under the concentration-time curve (AUC) of DMY in the DMY-SEDDS group was 4.13-fold higher than in the DMY suspension group. Furthermore, treatment with DMY-SEDDS significantly enhanced the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver of mice (p < 0.05). Interestingly, DMY-SEDDS also increased ADH activity in the stomach of mice with alcoholism (p < 0.01), thereby enhancing ethanol metabolism in the gastrointestinal tract and reducing ethanol absorption into the bloodstream. As a result, the blood alcohol concentration of mice with alcoholism was significantly decreased after DMY-SEDDS treatment (p < 0.01). In the acute alcoholism mice model, compared to saline treatment, DMY-SEDDS prolonged the onset of LORR (loss of righting reflex) (p < 0.05) and significantly shortened the duration of LORR (p < 0.01). Additionally, DMY-SEDDS treatment significantly reduced gastric injury in acute alcoholism mice. Collectively, these findings demonstrate the potential of DMY-SEDDS as a treatment in the treatment of alcoholism.
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spelling pubmed-105352662023-09-29 Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect Dong, Jianxia Wang, Shu Mao, Jiamin Wang, Zhidan Zhao, Shiying Ren, Qiao Kang, Jialing Ye, Jing Xu, Xiaohong Zhu, Yujin Zhang, Quan Pharmaceutics Article Intraperitoneal injection of dihydromyricetin (DMY) has shown promising potential in the treatment of alcoholism. However, its therapeutic effect is limited due to its low solubility, poor stability, and high gut-liver first-pass metabolism, resulting in very low oral bioavailability. In this study, we developed a DMY-loaded self-emulsifying drug delivery system (DMY-SEDDS) to enhance the oral bioavailability and anti-alcoholism effect of DMY. DMY-SEDDS improved the oral absorption of DMY by facilitating lymphatic transport. The area under the concentration-time curve (AUC) of DMY in the DMY-SEDDS group was 4.13-fold higher than in the DMY suspension group. Furthermore, treatment with DMY-SEDDS significantly enhanced the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver of mice (p < 0.05). Interestingly, DMY-SEDDS also increased ADH activity in the stomach of mice with alcoholism (p < 0.01), thereby enhancing ethanol metabolism in the gastrointestinal tract and reducing ethanol absorption into the bloodstream. As a result, the blood alcohol concentration of mice with alcoholism was significantly decreased after DMY-SEDDS treatment (p < 0.01). In the acute alcoholism mice model, compared to saline treatment, DMY-SEDDS prolonged the onset of LORR (loss of righting reflex) (p < 0.05) and significantly shortened the duration of LORR (p < 0.01). Additionally, DMY-SEDDS treatment significantly reduced gastric injury in acute alcoholism mice. Collectively, these findings demonstrate the potential of DMY-SEDDS as a treatment in the treatment of alcoholism. MDPI 2023-09-08 /pmc/articles/PMC10535266/ /pubmed/37765265 http://dx.doi.org/10.3390/pharmaceutics15092296 Text en © 2023 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
Dong, Jianxia
Wang, Shu
Mao, Jiamin
Wang, Zhidan
Zhao, Shiying
Ren, Qiao
Kang, Jialing
Ye, Jing
Xu, Xiaohong
Zhu, Yujin
Zhang, Quan
Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect
title Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect
title_full Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect
title_fullStr Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect
title_full_unstemmed Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect
title_short Preparation of Dihydromyricetin-Loaded Self-Emulsifying Drug Delivery System and Its Anti-Alcoholism Effect
title_sort preparation of dihydromyricetin-loaded self-emulsifying drug delivery system and its anti-alcoholism effect
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535266/
https://www.ncbi.nlm.nih.gov/pubmed/37765265
http://dx.doi.org/10.3390/pharmaceutics15092296
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