Microscopic Cascading Devices for Boosting Mucus Penetration in Oral Drug Delivery-Micromotors Nesting Inside Microcontainers.

Abstract

In the case of macromolecules and poorly permeable drugs, oral drug delivery features low bioavailability and low absorption across the intestinal wall. Intestinal absorption can be improved if the drug formulation could be transported close to the epithelium. To achieve this, a cascade delivery device comprising Magnesium-based Janus micromotors (MMs) nesting inside a microscale containers (MCs) has been conceptualized. The device aims at facilitating targeted drug delivery mediated by MMs that can lodge inside the intestinal mucosa. Loading MMs into MCs can potentially enhance drug absorption through increased proximity and unidirectional release. The MMs will be provided with optimal conditions for ejection into any residual mucus layer that the MCs have not penetrated. MMS confined inside MCs propel faster in the mucus environment as compared to non-confined MMs. Upon contact with a suitable fuel, the MM-loaded MC itself can also move. An in vitro study shows fast release profiles and linear motion properties in porcine intestinal mucus compared to more complex motion in aqueous media. The concept of dual-acting cascade devices holds great potential in applications where proximity to epithelium and deep mucus penetration are needed.