Editorial Feature

Recent Success for In-Human Drug Delivering Micromotors

Artificial micro and nanomotors have been a trending research topic within the biomedical industry as a means of transporting therapeutic materials to target organs in a rapid and efficient manner.

The terms micro and nanomotors refer to a class of micro and nanoscaled man-made devices that actively convert their energy source, which can include catalytic, magnetic or acoustic energy, to mechanical motions that self-propel these tiny machines and their cargo materials to their target destination1.

Following their previous success in achieving a successful performance of their zinc (Zn)-based and magnesium (Mg)-based micromotors under in vivo conditions, a group of Nanoengineers led by Professors Joseph Wang and Liangfang Zhang at the University of California San Diego have developed Mg-based micromotors that can successfully self-propel to deliver drugs within the gastrointestinal tract.          

Following their in vivo evaluation of artificial motors, which were powered on locally supplied fuels, in the mouse’s stomach, Drs. Zhang and Wang reported that the naturally occurring acid-driven movement of fluids within the stomach provides an ideal environment for the binding and retention of the micromotors, as well as their cargo materials, to remain on the stomach wall to ensure adequate drug delivery.

In fact, the gastric acid within the stomach gradually dissolves the body of the motors to release their materials, which eliminates the potential for any possible toxicity to be associated with this method of drug delivery2. Following their previous success, the Researchers built upon this study and applied Mg-based micromotors loaded with clarithromycin (CLR), an antibiotic that is used to treat and prevent infections, for the in vivo treatment of Helicobacter pylori (H. pylori). H. pylori, often referred to as “ulcer bacteria” is a species of bacterium that causes an infection and subsequent chronic inflammation of the stomach and duodenum. This extremely contagious infection affects approximately 50% of the world’s population, therefore the effective treatment and prevention of this illness is imperative as it has a 20% chance of recurrence3.

The core of the Mg-micromotors constructed by the UC San Diego team is comprised of Mg microparticles of an average size of approximately 20 micrometers (mm) that were individually coated with a thin layer of titanium dioxide (TiO2). The layer of TiO2 coating left a small opening on the surface of the Mg microparticles, which proved to be essential in allowing for the particles to allow for the gastric acid of the stomach to act as their fuel source. These Mg-TiO2 particles were then coated with a poly(lactic-co-glycolic acid) PLGA film that contained the CLR antibiotic payload.

Once the antibiotic was loaded, the microparticles were coated on their outermost positively charged layer of chitosan, a linear polysaccharide material that allowed for the adhesion of the micromotor to remain on the stomach wall4. Both H. pylori infected and non-infected mice were given oral gavage of either the Mg-based micromotors or distilled water at 30 minutes and 2 hours4.

To confirm functionality and adequate delivery of CLR through micromotor delivery, the Researchers took both bright field and fluorescence microscopic images of the luminal lining of the excised mouse stomachs.

The powerful propulsion of the Mg-micromotors by the gastric acid, and their ensuing penetration and binding to the stomach wall by their chitosan layer allows for the micromotor to adequately deliver CLR to the entire stomach. The efficient drug delivery performed by the Mg-micrometers significantly reduced the presence of the H. pylori infection within the stomach without involving the use of proton pump inhibitors (PPIs), which are commonly used in the clinical treatment of H. pylori.

The complete lack of adverse toxicological effects associated with the oral administration of Mg-micromotors allows this biocompatible material to be a realistic therapeutic option for future drug delivery endeavors.

Image Credit:

GiroScience/ Shutterstock.com

References:

  1. “Micro and nanomotors in diagnostics” A. Chalupniak, E. Narvaez, et al. Advanced Drug Delivery Reviews. (2015). DOI: 10.1016/j.addr.2015.09.004.
  2. “Artificial Micromotors in the Mouse’s Stomach: A Step toward in Vivo Use of Synthetic Motors” W. Gao, R. Song, et al. ACS Nano. (2015). DOI: 10.1021/nn507097k.
  3. “H. pylori (Helicobacter Pylori) Infection” – MedicineNet.com
  4. “Micromotor-enabled active drug delivery for in vivo treatment of stomach infection” B. Esteban-Fernandez de Avila, P. Angsantiful, et al. Nature Communications (2017). DOI: 10.1038/s41467-017-00309-w.

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Benedette Cuffari

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018. During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine, which are two nitrogen mustard alkylating agents that are currently used in anticancer therapy.

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