Cheerios Effect Inspired Microbubbles as Suspended and Adhered Oral Delivery Systems

Abstract

Oral drug administration has an important role in medical treatment. Attempts to develop drug microcarriers with desired features for extended duration and improved absorption is highly sought. Herein, inspired by the physical phenomenon of the Cheerios effect, a novel microfluidic electrospray microbubble carrier is presented that can suspend and actively adhere to the stomach for durable oral delivery. Compared with conventional fabrication methods, the present strategy shows stability and controllability of the product. Benefiting from their uniform hollow structure, the resultant microbubbles present the same behavior of the Cheerios and can float in the gastric juice, adhere and remain to the stomach wall, which thus enhance the duration and absorption of the loaded drugs. Based on these, it is demonstrated as a proof of concept that the dexamethasone‐loaded hollow microbubbles can be applied to oral administration and remain suspended and adhered to the stomach of murine for more than 1 d, showing good therapeutic effect in treating lupus erythematosus. Thus, it is believed that the microbubbles floating system will find important values in long‐term oral administration.

Bioinspired oral delivery devices

“…To avoid clearance, the devices need to adhere to the GI tract 26,98 , in particular through wet adhesion because the digestive tract is rich in mucus and digestive fluid. Microscale and nanoscale structures can be applied 132,133 or, alternatively, adhesive chemical components 134 can be added to the delivery device to enhance wet adhesion by generating mechanical interlocking, negative pressure and topological adhesion. For example, spike-like structures can be implemented to prolong retention time, inspired by the structures of parasitic worms that can live in the GI tract for years.…”

“…Bioinspired oral delivery devices can be fabricated into various types of formulations and dosage forms, including capsules 148 , tablets 149 , nanoparticles 145 , microspheres 5 , bubbles 133 , films 1 , coatings 138 and sprays 39 , depending on their composition, structure and application. Tablets are typically formed by compressing or moulding 8,149 , and capsules are prepared by filling drug substances into a hard gelatin shell followed by sealing and polishing 8,149 (Box 1).…”

Applications of capillary action in drug delivery

“…A controlled drug delivery system with prolonged residence time in the stomach and bladder is of great practical importance for drug absorption. Floating microspheres-controlled drug delivery systems achieve iScience Review long-term gastric retention up to 24 hr or longer (Bhadouriya et al, 2011;Zhao et al, 2021). On the other hand, the drug release from the floating microspheres is required to last for 24 hr to take full advantage of the long retention period.…”

Recent advances in liver‐on‐chips: Design, fabrication, and applications

“…By controlling the type and proportion of cells cultured, the chips can more accurately mimic the real liver. Additionally, microfluidic technologies, which use the microfluidic devices with microchannels and can regulate fluids in microscale precisely, 28–59 are often employed to construct the chips, 60–66 and they can not only supply nutrients and excrete metabolites but also provide shear force for the cultured cells. Relative to traditional culture methods, hepatocytes can maintain phenotypes for longer periods of time, enabling previously elusive functions such as microstructural mimicry of liver sinusoids, hepatic lobules, and integration of multiple organ functions.…”