Journal
BIOACTIVE MATERIALS
Volume 9, Issue -, Pages 54-62Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.08.004
Keywords
Micro- and nanomotors; Polydopamine; Urease; Oral delivery; Stomach diseases
Funding
- Basic Science Research Program of the National Research Foundation (NRF) - Ministry of Science and ICT, Korea [2020R1A2C3014070]
- Korea Medical Device Development Fund grant of the National Research Foundation (NRF) - Ministry of Science and ICT, Korea [2020M3E5D8105732]
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Ministry of Science and ICT, Korea [2021M3E5E7021473]
- Engineering Research Center (ERC) Program of the National Research Foundation (NRF) - Ministry of Science and ICT, Korea [NRF-2017R1A5A1014708]
- National Research Foundation of Korea [2020R1A2C3014070, 2021M3E5E7021473] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This study developed a bioinspired enzyme-powered biopolymer micromotor that converts urea to ammonia to facilitate its penetration into the stomach tissue layer. The successful fabrication of micromotors was confirmed and they showed enhanced penetration and prolonged retention in the stomach. Furthermore, the micromotors did not cause any toxicity in the GI tract.
Self-propelling micro- and nano-motors (MNMs) have been extensively investigated as an emerging oral drug delivery carrier for gastrointestinal (GI) tract diseases. However, the propulsion of current MNMs reported so far is mostly based on the redox reaction of metals (such as Zn and Mg) with severe propulsion gas generation, remaining non-degradable residue in the GI tract. Here, we develop a bioinspired enzyme-powered biopolymer micromotor mimicking the mucin penetrating behavior of Helicobacter pylori in the stomach. It converts urea to ammonia and the subsequent increase of pH induces local gel-sol transition of the mucin layer facilitating the penetration into the stomach tissue layer. The successful fabrication of micromotors is confirmed by high-resolution transmission electron microscopy, electron energy loss spectroscopy, dynamic light scattering analysis, zeta-potential analysis. In acidic condition, the immobilized urease can efficiently converted urea to ammonia, comparable with that of neutral condition because of the increase of surrounding pH during propulsion. After administration into the stomach, the micromotors show enhanced penetration and prolonged retention in the stomach for 24 h. Furthermore, histological analysis shows that the micromotors are cleared within 3 days without causing any toxicity in the GI tract. The enhanced penetration and retention of the micromotors as an active oral delivery carrier in the stomach would be successfully harnessed for the treatment of various GI tract diseases.
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