# Magnetic drug-loaded microbubbles for treating lower limb venous thrombosis under controllable rotating magnetic field

## TL;DR

This study introduces magnetic microbubbles loaded with a clot-dissolving drug to treat leg blood clots using a rotating magnetic field, showing improved effectiveness in both lab and animal tests.

## Contribution

A novel magnetic drug delivery system using microbubbles and a rotating magnetic field for enhanced thrombolysis in acute venous thrombosis.

## Key findings

- Magnetic microbubbles achieved 25% thrombolysis in vitro under a 1.5 mT rotating magnetic field.
- In vivo experiments in rabbits showed restored blood flow and elevated D-dimer levels, indicating effective clot dissolution.
- The system reached a maximum proUK encapsulation efficiency of 56.65% at 7.5 mg/mL concentration.

## Abstract

This study aimed to develop a poly (lactic-co-glycolic acid) (PLGA)-based magnetic loaded iron oxide (Fe3O4) and single-chain urokinase-type plasminogen activator (proUK) for enhancing thrombolysis under a controlled rotating magnetic field, specifically targeting acute lower limb venous thrombosis.

Acute thrombotic disorders are significant health threats, however, the exploration of magnetic actuation as a treatment for acute thrombosis has been limited.

Magnetic microbubbles were prepared using a double emulsion method, loaded with Fe3O4 nanoparticles and proUK. The microbubble characteristics were analyzed through chemical, physical, and biological related technologies.

Fe3O4 nanoparticle loading was confirmed by X-ray diffraction, and the encapsulation efficiency of the magnetic microbubbles was determined using an ELISA kit and colorimetric assay, reaching a maximum of 56.65% at a proUK concentration of 7.5 mg/mL. Thrombolysis efficiency was significantly enhanced under a rotating magnetic field of 1.5 mT and 6 Hz frequency, achieving up to 25% lysis rate in vitro, markedly higher than control conditions. Furthermore, in vivo experiments using a rabbit model of hindlimb venous thrombosis validated the efficacy of this approach, with Color Doppler Flow Imaging showing restored blood flow and elevated D-dimer levels indicating effective thrombus dissolution.

This novel magnetic drug delivery system, combined with a rotating magnetic field, demonstrates excellent thrombolysis efficiency and presents a promising and safe therapeutic strategy for acute venous thrombosis.