Characterization of magnetically driven colloidal microwheels and their fibrinolytic applications

Abstract

Colloids carrying payloads of medication have become a popular drug delivery approach. Since it is not always possible to rely on blood circulation to distribute the colloids to the target site in the body, researchers seek to develop methods of controlling colloid movement. We advance the development of a magnetic system that moves colloids using a canted rotating magnetic field. Beads containing superparamagnetic iron oxide crystals assemble into wheel-like structures that rotate in alignment with the field and roll via wet friction along adjacent surfaces. These micro-wheels (μwheels) are suitable for drug delivery. We utilize μwheels to deliver tissue plasminogen activator (tPA) to a blood clot. tPA can be used to treat stroke but is rarely used because it can cause hemorrhaging. We show that μwheels functionalized with tPA combine mechanical and biochemical mechanisms to achieve enhanced fibrinolysis over that of soluble tPA at therapeutic concentrations. μwheels conjugated with an effective tPA concentration of 3.6 μg/mL degrade fibrin twofold faster than soluble tPA at 10 μg/mL. μwheels are an effective fibrinolytic because of their ability to target, penetrate into and concentrate at a clot. Here, we show that μwheels powered by a magnetic field are capable of exiting a laminar flow field and entering a connecting blocked channel. These experiments suggest that the μwheel translational mechanism is robust enough to navigate vasculature in order to target occlusions. Finally, we use total internal reflection microscopy (TIRM) to characterize the mechanism of μwheel translation. A sphere translating against a glass slide under influence of the magnetic field is 89 ± 39 nm from the slide. The gap distance can be affected by changing the load force on the μwheel or electrochemical interactions between the μwheel and surface, suggesting that μwheel interactions with vasculature will be tunable. The μwheels used herein are a novel and exciting drug delivery system whose potential applications are not limited to treating stroke.