A self-triggering and fully sustainable gastric device enabling long-acting oral delivery of macromolecules
Long-acting oral delivery of macromolecular therapeutics remains difficult, as most oral delivery devices focus on improving gastrointestinal absorption but do not adequately address sustained drug release and frequent dosing. In parallel, many gastric-retentive systems rely on nondegradable structural components, raising concerns regarding retained-device burden and postuse medical waste. Here, we report a biodegradable oral capsule device for long-lasting drug delivery, termed the sustainable gastric self-triggered device (SGSTD), inspired by the stinging mechanism of Apis mellifera . After reaching the stomach, SGSTD autonomously deploys a biodegradable barbed drug-loaded needle into the gastric wall, while the remaining carrier body is subsequently excreted, establishing a bioinspired “deploy-and-separate” strategy for long-acting gastric delivery. The embedded needle enables microchannel-mediated sustained release, with structurally tunable release behavior. Ex vivo and in vivo porcine studies confirmed gastric deployment, tissue retention, systemic safety, and localized tissue repair around the insertion region. In vivo, SGSTD maintained insulin delivery for over 7 days, achieving a relative bioavailability of 63.8%, approximately 17.2-fold higher than conventional oral administration. SGSTD is cost-effective, scalable, and composed of biodegradable materials, providing a sustainable strategy for long-acting oral biologics delivery.
Authors
- Yiyuan Yang (ORCID: https://orcid.org/0000-0003-1262-354X)
- Weixuan Liu (ORCID: https://orcid.org/0000-0002-8079-1089)
- U Kei Cheang (ORCID: https://orcid.org/0000-0002-2324-6391)
- Tianyuan Ci (ORCID: https://orcid.org/0000-0002-2887-3642)
- Kewen Lei (ORCID: https://orcid.org/0000-0002-3586-682X)
- Shuquan Cui (ORCID: https://orcid.org/0000-0002-8764-0718)
- Xiangyu Liang (ORCID: https://orcid.org/0000-0002-3663-8394)
- Yingning He (ORCID: https://orcid.org/0000-0002-5873-4520)
- Teng Dong (ORCID: https://orcid.org/0000-0002-6881-2350)
- Zede Yi (ORCID: https://orcid.org/0009-0003-7855-5575)
- Yancong Zhang (ORCID: https://orcid.org/0000-0002-2768-2975)
- Xianglin Wu
- Tian Liu (ORCID: https://orcid.org/0000-0001-9768-5496)
- Weijie Li (ORCID: https://orcid.org/0000-0001-5605-9579)
- Hongyan Yuan (ORCID: https://orcid.org/0000-0001-8225-0211)
- Yunxiang Zhang (ORCID: https://orcid.org/0000-0002-8886-975X)
- Haoying Wang (ORCID: https://orcid.org/0000-0002-9190-9978)
- Chengbang Lu
- Yue Zhao (ORCID: https://orcid.org/0009-0006-8862-8610)
- Kai Wu (ORCID: https://orcid.org/0009-0006-2360-5768)
- Yaoben Wang (ORCID: https://orcid.org/0009-0000-2784-026X)
Institutions
- University of Minnesota (US)
- Chongqing University (CN)
- University of California, Los Angeles (US)
- National University of Singapore (SG)
- Fudan University (CN)
- Dalian University of Technology (CN)
- Southern University of Science and Technology (CN)
- Agricultural Genomics Institute at Shenzhen (CN)
- Dalian University (CN)
- Institute of Bast Fiber Crops (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Guangzhou Mechanical Engineering Research Institute (China) (CN)
- Chinese University of Hong Kong, Shenzhen (CN)
- Chinese Academy of Agricultural Sciences (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- First People's Hospital of Chongqing (CN)
- University College London (GB)
- Xiangtan University (CN)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-08-28
- DOI
- https://doi.org/10.1126/sciadv.aef9186
- Primary Topic
- Hydrogels: synthesis, properties, applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Natural Science Foundation of Hunan Province