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Micromotor-enabled active drug delivery for in vivo treatment of stomach infection.

ABSTRACT: Advances in bioinspired design principles and nanomaterials have led to tremendous progress in autonomously moving synthetic nano/micromotors with diverse functionalities in different environments. However, a significant gap remains in moving nano/micromotors from test tubes to living organisms for treating diseases with high efficacy. Here we present the first, to our knowledge, in vivo therapeutic micromotors application for active drug delivery to treat gastric bacterial infection in a mouse model using clarithromycin as a model antibiotic and Helicobacter pylori infection as a model disease. The propulsion of drug-loaded magnesium micromotors in gastric media enables effective antibiotic delivery, leading to significant bacteria burden reduction in the mouse stomach compared with passive drug carriers, with no apparent toxicity. Moreover, while the drug-loaded micromotors reach similar therapeutic efficacy as the positive control of free drug plus proton pump inhibitor, the micromotors can function without proton pump inhibitors because of their built-in proton depletion function associated with their locomotion.Nano- and micromotors have been demonstrated in vitro for a range of applications. Here the authors demonstrate the in-vivo therapeutic use of micromotors to treat H. pylori infection.

SUBMITTER: de Avila BE

PROVIDER: S-EPMC5559609 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Micromotor-enabled active drug delivery for in vivo treatment of stomach infection.

de Ávila Berta Esteban-Fernández BE Angsantikul Pavimol P Li Jinxing J Angel Lopez-Ramirez Miguel M Ramírez-Herrera Doris E DE Thamphiwatana Soracha S Chen Chuanrui C Delezuk Jorge J Samakapiruk Richard R Ramez Valentin V Obonyo Marygorret M Zhang Liangfang L Wang Joseph J

Nature communications 20170816 1

Advances in bioinspired design principles and nanomaterials have led to tremendous progress in autonomously moving synthetic nano/micromotors with diverse functionalities in different environments. However, a significant gap remains in moving nano/micromotors from test tubes to living organisms for treating diseases with high efficacy. Here we present the first, to our knowledge, in vivo therapeutic micromotors application for active drug delivery to treat gastric bacterial infection in a mouse ...[more]

PMID: 28814725

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Project description: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. Graphical abstract Image 1 Highlights • 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.

Dataset Information

Micromotor-enabled active drug delivery for in vivo treatment of stomach infection.

Publications

Micromotor-enabled active drug delivery for in vivo treatment of stomach infection.

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