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.

The highly acidic gastric environment creates a physiological barrier for using therapeutic drugs in the stomach. While proton pump inhibitors have been widely used for blocking acid-producing enzymes, this approach can cause various adverse effects. Herein, we report on a new microdevice, consisting of magnesium-based micromotors that can autonomously and temporally neutralize gastric acid through efficient chemical propulsion in the gastric fluid by rapidly depleting the localized protons. Coating these micromotors with a cargo-containing pH-responsive polymer layer leads to autonomous release of the encapsulated payload upon gastric-acid neutralization by the motors. Testing in a mouse model, the in vivo results demonstrate that these motors can safely and rapidly neutralize gastric acid and simultaneously release payload without causing noticeable acute toxicity or affecting the stomach function, with the normal stomach pH restored within 24 h post motor administration.

A rapid and efficient micromotor-based bacteria killing strategy is described. The new antibacterial approach couples the attractive antibacterial properties of chitosan with the efficient water-powered propulsion of magnesium (Mg) micromotors. These Janus micromotors consist of Mg microparticles coated with the biodegradable and biocompatible polymers poly(lactic-co-glycolic acid) (PLGA), alginate (Alg) and chitosan (Chi), with the latter responsible for the antibacterial properties of the micromotor. The distinct speed and efficiency advantages of the new micromotor-based environmentally friendly antibacterial approach have been demonstrated in various control experiments by treating drinking water contaminated with model Escherichia coli (E. coli) bacteria. The new dynamic antibacterial strategy offers dramatic improvements in the antibacterial efficiency, compared to static chitosan-coated microparticles (e.g., 27-fold enhancement), with a 96% killing efficiency within 10 min. Potential real-life applications of these chitosan-based micromotors for environmental remediation have been demonstrated by the efficient treatment of seawater and fresh water samples contaminated with unknown bacteria. Coupling the efficient water-driven propulsion of such biodegradable and biocompatible micromotors with the antibacterial properties of chitosan holds great considerable promise for advanced antimicrobial water treatment operation.

High intensity ultrasound irradiation was used to convert beta-chitin (BCHt) into chitosan (CHs). Typically, beta-chitin was suspended in 40% (w/w) aqueous sodium hydroxide at a ratio 1/10 (gmL(-1)) and then submitted to ultrasound-assisted deacetylation (USAD) during 50min at 60°C and a fixed irradiation surface intensity (52.6Wcm(-2)). Hydrogen nuclear magnetic resonance spectroscopy and capillary viscometry were used to determine the average degree of acetylation (DA‾) and viscosity average degree of polymerization (DPv‾), respectively, of the parent beta-chitin (DA‾=80.7%; DPv‾=6865) and USAD chitosans. A first USAD reaction resulted in chitosan CHs1 (DA‾=36.7%; DPv‾=5838). Chitosans CHs2 (DA‾=15.0%; DPv‾=5128) and CHs3 (DA‾=4.3%; DPv‾=4889) resulted after repeating the USAD procedure to CHs1 consecutively once and twice, respectively. Size-exclusion chromatography analyzes allowed the determination of the weight average molecular weight (Mw‾) and dispersity (Ð) of CHs1 (Mw‾=1,260,000gmol(-1); Ð=1.4), CHs2 (Mw‾=1,137,000gmol(-1); Ð=1.4) and CHs3 (Mw‾=912,000gmol(-1); Ð=1.3). Such results revealed that, thanks to the action of high intensity ultrasound irradiation, the USAD process allowed the preparation of unusually high molecular weight, randomly deacetylated chitosan, an important breakthrough to the development of new high grade chitosan-based materials displaying superior mechanical properties.

Ultrasound‐assisted deacetylation (USAD) produces chitosan by treating beta‐chitin suspended in 40% aqueous sodium hydroxide with high‐intensity ultrasound irradiation. Chitosans resulting from the application of non‐isothermal and isothermal USAD processes were characterized using NMR spectroscopy, X‐ray diffraction, scanning electron microscopy, viscosity measurements and size‐exclusion chromatography. The characteristics of the USAD‐produced chitosan strongly depend on the processing temperature and ultrasound parameters, namely the irradiation amplitude and duration, with viscosity‐average molecular weight in the range 100 000–750 000 g mol−1 and average degree of acetylation in the range 6.0–25.0%. Moreover, appropriate adjustment of the USAD parameters allows the production of chitosan with high molecular weight (Mw ≈ 106 g mol−1) and low degree of acetylation (ca 7.0%) after a single‐step short‐time processing (30 min) carried out at low to moderate temperature (50–80 °C). The occurrence of cavitation, a phenomenon whose intensity depends on the irradiation amplitude and duration as well as on the processing temperature, is responsible for reducing the average size of the polysaccharide particles, favoring the accessibility of sodium hydroxide to the reactive sites and supporting a more efficient deacetylation of beta‐chitin as compared to the thermochemical process. Copyright © 2011 Society of Chemical Industry

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