Convenient, cost-effective and with high rates of patient compliance, the oral route has and will continue to be one of the most popular options for drug delivery, but for vaccines the oral route has proven challenging. Although some oral vaccines can stimulate immune cells in mucus layer of the intestine to produce IgA (a class of antibody), for the most part the insufficient potency of oral vaccines has prevented them from conferring ample protection against pathogens. In an effort to overcome these limitations, researchers at the University of San Diego have developed oral vaccines with a twist - they are powered by micromotors to target the mucus layer of the intestine (1).
“We hypothesized that by using micromotor technology to add active propulsion to oral vaccines, we could facilitate enhanced processing of vaccines by the immune system. This would, in turn, would generate a much stronger immune response (in the form of higher antibody levels) compared with formulations that lack propulsion,” explains Ronnie Fang, Assistant Project Scientist in the Department of NanoEngineering at UC San Diego.
The motor vaccine formulation developed by the La Jolla based team consists of several components, but at the heart of the drug is a magnesium core coated in titanium dioxide used to propel the vaccine.
“The titanium coating on the core is placed asymmetrically allowing one side of the magnesium core to be exposed to interact with the biological fluids that power the motors,” explains Fang. “The motor core is then coated with a layer of red blood cell membrane to help cue the immune system and allow it to illicit appropriate responses.”
To allow the motor cores to adhere to the intestinal wall lining and protect them from succumbing to the harsh environment of the stomach, the researchers added additional chitosan and enteric polymer layers to coat their molecules. The team were able to successfully feed their formulation to mice and found that the propulsion mechanism they had devised enabled better retention of the vaccine material on the intestine wall and greater amounts of antibody when compared to static microparticles.
The positive results have encouraged the team to move their work beyond a proof-of-concept. They believe that the concept of motor-based vaccines should be able to apply to any type of infectious disease, once its safety in humans has been tested.
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References
- Liangfang Zhang et al., “Biomimetic Micromotor Enables Active Delivery of Antigens for Oral Vaccination”, Nano Lett. 1914-1921 (2019).
