Chemotaxis-based smart drug delivery of epirubicin using a 3D printed microfluidic chip

Abstract

Recent developments on self-propelled microdroplets, moving controllably in response to an external stimulus like chemical, electrical, or magnetic field, have opened a new horizon for smart drug delivery investigations. On the other hand, the new achievements in 3D printing technology has provided a promising option for the fabrication of microfluidic devices, which is an unrivalled platform for in-vitro drug delivery studies. By synergizing the features of chemotaxis, 3D printing, and microfluidic techniques a new approach was introduced to deliver the drug to targeted sites with a well-controlled method and a reasonable speed. A self-propelled ionic liquid ([P6,6,6,14][Cl]) microdroplet, as the drug carrier, was utilised for the targeted delivery of epirubicin anticancer drug within an integrated drug delivery microfluidic system. The asymmetric diffusion of [P6,6,6,14]+ ion from the microdroplet into an aqueous solution with chloride gradient concentration (created under an external electrical field) caused the microdroplet to move. The spatial and temporal position of the moving microdroplet could be controlled by changing the magnitude and polarity of the external electrical field. A piece of hollow-fiber, fixed next to the anode, was filled with phosphate buffer (as the receptor) and used to remove the drug from the carrier. The receptor solution was then taken and injected into a HPLC system for quantification of the released drug. After one-at-a-time optimization of the channel geometry and electrolyte concentration, the experimental variables affecting the drug loading including contact time, pH, and volume of carrier were optimized via a central composite design (CCD) approach.