Biomimetic Micromotor Enables Active Delivery of Antigens for Oral Vaccination

Abstract

Vaccination represents one of the most effective means of preventing infectious disease. In order to maximize the utility of vaccines, highly potent formulations that are easy to administer and promote high patient compliance are desired. In the present work, a biomimetic self-propelling micromotor formulation is developed for use as an oral antivirulence vaccine. The propulsion is provided by a magnesium-based core, and a biomimetic cell membrane coating is used to detain and neutralize a toxic antigenic payload. The resulting motor toxoids leverage their propulsion properties in order to more effectively elicit mucosal immune responses. After demonstrating the successful fabrication of the motor toxoids, their uptake properties are shown in vitro. When delivered to mice via an oral route, it is then confirmed that the propulsion greatly improves retention and uptake of the antigenic material in the small intestine in vivo. Ultimately, this translates into markedly elevated generation of antibody titers against a model toxin. This work provides a proof-of-concept highlighting the benefits of active oral delivery for vaccine development, opening the door for a new set of applications in which biomimetic motor technology can provide significant benefits.

Recent Advances in Nano‐ and Micromotors

“…They demonstrated drug enhancement and retention by reductions in the bacterial burden in harvested stomachs, going from 3 × 10 6 to 2.9 × 10 5 colony forming unit (CFU) g −1 when CLR was delivered in silica particles (controls) or the micromotors, respectively. In a recent effort, Mg‐TiO 2 core–shell asymmetric structures were coated with red blood cell membranes and loaded with a bacteria toxin, followed by a chitosan layer and a terminating Eudragit L100‐55 coating . When these toxoid‐micromotors were orally administered to mice, Eudragit protected the micromotors in the stomach and the Mg core was only exposed in the intestine.…”

“…A‐i) Bubble‐propelled trajectories and ii) determined speed of partially, completely, or noncoated Mg‐TiO 2 motor toxoids (MT) in gastric and intestinal fluids. Reproduced with permission . 2019, American Chemical Society.…”

Robotics in the Gut

“…Furthermore, the distance traveled in GI tract before propulsion can be controlled by tuning the thickness of the enteric coating. Following this work, a therapeutic investigation of the enteric micromotors was carried out by coating of red blood cell membrane to enhanced generation of mucosal immunity . Compared with the conventional passive delivery, the microrobots with active motion and enteric coating elevated the retention and uptake of antigenic material, opening a new door for active oral delivery for the development of vaccine.…”

Biomaterial Approaches for Understanding and Overcoming Immunological Barriers to Effective Oral Vaccinations

“…A micromotor device was coated with a toxin antigen inserted within red blood cell membrane (RBCtoxin) that was further coated with chitosan and enveloped in Eudragit L100-55 ( Figure 7A). [112] Here, a small opening in the nanoparticle gives access to the Mg-based micromotor core that undergoes macrogalvanic corrosion in gastric acid to generate hydrogen gas as a propellant. [113] The propulsion reaction consumes protons and produces hydroxide to effectively neutralize local acidity and trigger phase-transition of the pH-responsive Eudragit for cargo release.…”