Multicompartment Tubular Micromotors Toward Enhanced Localized Active Delivery

Abstract

A tubular micromotor with spatially resolved compartments is presented towards efficient sitespecific cargo delivery, with a back-end zinc (Zn) propellant engine segment and an upfront cargo-This article is protected by copyright. All rights reserved. 2 loaded gelatin segment further protected by a pH-responsive cap. The multi-compartment micromotors display strong gastric-powered propulsion with tunable lifetime depending on the Zn segment length. Such propulsion significantly enhances the motor distribution and retention in the gastric tissues, by pushing and impinging the front-end cargo segment onto the stomach wall. Once the micromotor penetrates the gastric mucosa (pH ≥ 6.0), its pH-responsive cap dissolves, promoting the autonomous localized cargo release. The fabrication process, physicochemical properties, and propulsion behavior are systematically tested and discussed. Using a mouse model, the multicompartment motors, loaded with a model cargo, demonstrate a homogeneous cargo distribution along with ~4-fold enhanced retention in the gastric lining compared to mono-compartment motors, while showing no apparent toxicity. Therapeutic payloads can also be loaded into the pH-responsive cap, in addition to the gelatin-based compartment, leading to concurrent delivery and sequential release of dual cargos towards combinatorial therapy. Overall, this multi-compartment micromotor system provides unique features and advantages that will further advance the development of synthetic micromotors for active transport and localized delivery of biomedical cargos.

The Future Application of Organ-on-a-Chip Technologies as Proving Grounds for MicroBioRobots

“…Here, a compartmentalized MBR would be used. It would contain a cargo-carrying cap, similar to the previously described work of Esteban-Fernandez de Avila et al ( Figure 4 C) [ 46 ]. For in vivo applications, the MBR’s cargo-carrying cap could even be functionalized to target the endothelial lining of the pulmonary vasculature, and would only release the contained Cpd22 upon detection of chemical markers indicating penetration of the extracellular matrix and localization with the fusion with the contained SMCs [ 45 ].…”

“…Schuerle et al used helical swimming microrobots to enhance convective transport of fluorescent nanoparticles across a vessel–matrix interface representative of blood vessel extravasation ( Figure 4 B) [ 45 ]. Alternately, Esteban-Fernandez de Avila et al created an active transport-based system and incorporated a propulsive motor in a multicompartment microstructure to aid in physically penetrating a tissue barrier ( Figure 4 C) [ 46 ]. In this case, the drug of interest was encapsulated in a pH-responsive cap, which only began to dissolve upon penetration of the tissue lining, which exposed the cap to an increased pH.…”

“…( C ) In another example of enhancing barrier permeability, ( i ) multicompartment microbiorobots demonstrated localized, permeable cargo delivery by utilizing a micromotor as a propulsion system to penetrate tissue surfaces [ 46 ]. ( ii ) Polymer-capped-cargo was visualized via SEM imaging and fluorescent imaging to depict ( iii ) dissolution and ( iv ) cargo release [ 46 ]. Images reproduced with permission from Esteban-Fernandez de Avila et al Advanced Materials , 2020.…”

Zinc Microrocket Pills: Fabrication and Characterization toward Active Oral Delivery

“…These findings are consistent with the results derived from previous toxicity studies using Zn-based microrockets in the same mouse model. [13,14] Overall, the in vivo toxicity studies of Zn microrocket pills showed no apparent alteration of GI histopathology and no observable inflammation, suggesting that the pill treatment at the administered Zn microrocket dosage is safe in mice. It is important to mention that increasing the content of Zn microrockets beyond 10% might produce abnormal GI inflammation due to excessive H 2 gas generation.…”

“…[11] Different designs of such acid-powered Znmicrorockets have demonstrated efficient cargo-loading capacity with autonomous release. [12,13] One of the key advantages of Zn-based microrockets is the biodegradability of the motor body, which completely dissolves and disappears in acidic conditions, thus leaving no harmful products behind. Such biodegradable behavior along with efficient propulsion in the gastric fluid has led to the first in vivo demonstration of Zn-based microrockets in a mouse model, illustrating a greatly enhanced retention of the payloads in the stomach lining without causing toxic effects.…”