Micromotor Pills as a Dynamic Oral Delivery Platform

Abstract

Tremendous progress has been made during the past decade toward the design of nano/micromotors with high biocompatibility, multifunctionality, and efficient propulsion in biological fluids, which collectively have led to the initial investigation of in vivo biomedical applications of these synthetic motors. Despite these recent advances in micromotor designs and mechanistic research, significant effort is needed to develop appropriate formulations of micromotors to facilitate their in vivo administration and thus to better test their in vivo applicability. Herein, we present a micromotor pill and demonstrate its attractive use as a platform for in vivo oral delivery of active micromotors. The micromotor pill is comprised of active Mg-based micromotors dispersed uniformly in the pill matrix, containing inactive (lactose/maltose) excipients and other disintegration-aiding (cellulose/starch) additives. Our in vivo studies using a mouse model show that the micromotor pill platform effectively protects and carries the active micromotors to the stomach, enabling their release in a concentrated manner. The micromotor encapsulation and the inactive excipient materials have no effects on the motion of the released micromotors. The released cargo-loaded micromotors propel in gastric fluid, retaining the high-performance characteristics of in vitro micromotors while providing higher cargo retention onto the stomach lining compared to orally administrated free micromotors and passive microparticles. Furthermore, the micromotor pills and the loaded micromotors retain the same characteristics and propulsion behavior after extended storage in harsh conditions. These results illustrate that combining the advantages of traditional pills with the efficient movement of micromotors offer an appealing route for administrating micromotors for potential in vivo biomedical applications.

Recent Advancements in Using Polymers for Intestinal Mucoadhesion and Mucopenetration

“…They coated magnesium‐based micromotors62 with a tuneable polymer layer that would only be soluble in neutral/alkaline environment aiming for the control over tissue penetration and retention at desired regions of the gastro‐intestinal tract, that is, the micromotors were found further down the intestine for thicker polymer coatings (Figure 4b). 63 More recently, they entrapped a magnesium‐based micromotors into a lactose/maltose pill matrix and illustrated that these micromotors exhibited better retention in a mouse stomach compared to the controls including the free micromotors 64…”

Multigear Bubble Propulsion of Transient Micromotors

“…In an attempt to move away from toxic fuels, expensive catalysts, and nondegradable leftovers, a push towards biofriendly materials has begun in recent years in the micromotor community [15,16]. To incorporate biodegradability for in vitro and in vivo applications, these micromotors are powered by the consumption of active metals, such as magnesium (Mg), zinc, and iron, which react with biofluids or seawater [17][18][19][20][21][22]. These micromotors self-propel via single replacement reactions in gastric acid, or via reaction with water in intestinal fluid, salty buffer solutions, or basic buffer solutions where the counter ions aid in removing the passivating byproduct layer of magnesium hydroxide [16].…”

“…The ability of Mg-based micromotors to propel in biological fluids with minimal risk has enabled their use for important applications, such as drug delivery, where micromotors outperform passive diffusion-based methods [17][18][19][20]23]. To fine tune the performance of these micromotors and provide design principles, it is crucial to understand their dynamics and the underlying mechanisms of motion.…”

A Light‐Driven Micromotor with Complex Motion Behaviors for Controlled Release

“…Micromotors are unique micrometer‐sized devices that can move inside a solution and accomplish various kinds of missions, making them potentially attractive in a wide range of potential applications in the field of sensing, environmental remediation, targeted delivery, etc. In order to realize the motion behavior, the structure of a micromotor has to be made asymmetric.…”