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

Author:

Wang Siqi1ORCID,Wang Yuqiong23,Lin Long45,Li Zongjie6,Liu Fengyi5,Zhu Long5,Chen Jie7,Zhang Nianrong1,Cao Xinyu1,Ran Sunman1,Liu Genzheng1,Gao Peng8,Sun Weiliang9,Peng Liang9,Zhuang Jian5,Meng Hua1ORCID

Affiliation:

1. Department of General Surgery and Obesity and Metabolic Disease Center China–Japan Friendship Hospital Beijing 100029 China

2. Department of Mechanical and Automation Engineering The Chinese University of Hongkong Hongkong 999077 China

3. School of Biological Science and Medical Engineering Beihang University Beijing 100191 China

4. Engineering College of Peking University Peking university Beijing 100029 China

5. School of Mechanical and Electrical Engineering Beijing University of Chemical Technology Beijing 100029 China

6. Shanghai Veterinary Research Institute Chinese Academy of Agricultural Science Shanghai 200241 China

7. Department of Ultrasound China–Japan Friendship Hospital Beijing 100029 China

8. Department of Clinical Laboratory China–Japan Friendship Hospital Beijing 100029 China

9. Institute of Clinical Medical Sciences China–Japan Friendship Hospital Beijing 100029 China

Abstract

AbstractThe 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.

Funder

Natural Science Foundation of Beijing Municipality

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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