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Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement

The rising incidence of health‐endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX‐A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer‐specific delivery strategy enabled by dissolving mi...

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Detalles Bibliográficos
Autores principales: Wang, Siqi, Wang, Yuqiong, Lin, Long, Li, Zongjie, Liu, Fengyi, Zhu, Long, Chen, Jie, Zhang, Nianrong, Cao, Xinyu, Ran, Sunman, Liu, Genzheng, Gao, Peng, Sun, Weiliang, Peng, Liang, Zhuang, Jian, Meng, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558648/
https://www.ncbi.nlm.nih.gov/pubmed/37552813
http://dx.doi.org/10.1002/advs.202300822
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author Wang, Siqi
Wang, Yuqiong
Lin, Long
Li, Zongjie
Liu, Fengyi
Zhu, Long
Chen, Jie
Zhang, Nianrong
Cao, Xinyu
Ran, Sunman
Liu, Genzheng
Gao, Peng
Sun, Weiliang
Peng, Liang
Zhuang, Jian
Meng, Hua
author_facet Wang, Siqi
Wang, Yuqiong
Lin, Long
Li, Zongjie
Liu, Fengyi
Zhu, Long
Chen, Jie
Zhang, Nianrong
Cao, Xinyu
Ran, Sunman
Liu, Genzheng
Gao, Peng
Sun, Weiliang
Peng, Liang
Zhuang, Jian
Meng, Hua
author_sort Wang, Siqi
collection PubMed
description The rising incidence of health‐endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX‐A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer‐specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX‐A and the resulting therapeutic effects. The drug‐loaded tips of the layer‐specific gastric paralysis microneedles (LGP‐MN) rapidly release and achieve uniform distribution of BTX‐A within the designated gastric wall layers. In an obesity rat model, the LGP‐MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06‐fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach‐derived glucagon‐like peptide‐1 due to the muscularis‐targeting LGP‐MN treatment is an important contributor to its unique glucose tolerance‐improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX‐A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP‐MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes.
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spelling pubmed-105586482023-10-08 Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement Wang, Siqi Wang, Yuqiong Lin, Long Li, Zongjie Liu, Fengyi Zhu, Long Chen, Jie Zhang, Nianrong Cao, Xinyu Ran, Sunman Liu, Genzheng Gao, Peng Sun, Weiliang Peng, Liang Zhuang, Jian Meng, Hua Adv Sci (Weinh) Research Articles The rising incidence of health‐endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX‐A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer‐specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX‐A and the resulting therapeutic effects. The drug‐loaded tips of the layer‐specific gastric paralysis microneedles (LGP‐MN) rapidly release and achieve uniform distribution of BTX‐A within the designated gastric wall layers. In an obesity rat model, the LGP‐MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06‐fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach‐derived glucagon‐like peptide‐1 due to the muscularis‐targeting LGP‐MN treatment is an important contributor to its unique glucose tolerance‐improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX‐A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP‐MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes. John Wiley and Sons Inc. 2023-08-08 /pmc/articles/PMC10558648/ /pubmed/37552813 http://dx.doi.org/10.1002/advs.202300822 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Wang, Siqi
Wang, Yuqiong
Lin, Long
Li, Zongjie
Liu, Fengyi
Zhu, Long
Chen, Jie
Zhang, Nianrong
Cao, Xinyu
Ran, Sunman
Liu, Genzheng
Gao, Peng
Sun, Weiliang
Peng, Liang
Zhuang, Jian
Meng, Hua
Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement
title Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement
title_full Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement
title_fullStr Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement
title_full_unstemmed Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement
title_short Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement
title_sort layer‐specific btx‐a delivery to the gastric muscularis achieves effective weight control and metabolic improvement
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558648/
https://www.ncbi.nlm.nih.gov/pubmed/37552813
http://dx.doi.org/10.1002/advs.202300822
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