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

文献类型： 外文期刊

第一作者： Wang, Siqi

作者： Wang, Siqi;Zhang, Nianrong;Cao, Xinyu;Ran, Sunman;Liu, Genzheng;Meng, Hua;Wang, Yuqiong;Wang, Yuqiong;Lin, Long;Lin, Long;Liu, Fengyi;Zhu, Long;Zhuang, Jian;Li, Zongjie;Chen, Jie;Gao, Peng;Sun, Weiliang;Peng, Liang

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关键词： botulinum neurotoxin A; glucagon-like peptide-1; microneedle patch; obesity; precise delivery

期刊名称：ADVANCED SCIENCE （ 影响因子：15.1； 五年影响因子：16.7 ）

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年卷期： 2023 年

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收录情况： SCI

摘要： 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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