Bioinspired urease-powered micromotor as an active oral drug delivery carrier in stomach

• Published in: Bioactive materials 2022-03, Vol.9, p.54-62
• Main Authors: Choi, Hyunsik, Jeong, Sang Hoon, Kim, Tae Yeon, Yi, Jeeyoon, Hahn, Sei Kwang
• Format: Article
• Language: English
• Subjects: Micro- and nanomotors; Oral delivery; Polydopamine; Stomach diseases; Urease
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2021.08.004

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. [Display omitted] •Polydopamine (PDA) hollow microcapsules are biocompatible, biodegradable, and muco-adhesive.•Urease-powered PDA micromotors are propelled by the decomposition of urea to ammonia and carbon dioxide.•Micromotors increase the local pH to induce the gel-sol transition of the mucus layer.•Micromotors result in enhanced penetration and prolonged retention in the stomach.•Micromotors can be effectively used for oral drug delivery with complete clearance from the GI tract.