Fabrication of ultrasound-responsive microbubbles via coaxial electrohydrodynamic atomization for triggered release of tPA

Abstract

A single-step fabrication method, coaxial electrohydrodynamic atomization (CEHDA), was developed to synthesize drug-loaded microbubbles (MBs) for combination treatment of ischemic stroke. The bioactivity of therapeutic agent (tPA, tissue plasminogen activator) after preparation was evaluated, showing that CEHDA could be very promising method for producing MBs with therapeutic functions. The bubble performance and tPA release profiles were also examined by exposing the bubbles to 2MHz ultrasound of various intensities. The results showed that the mean diameter of tPA-loaded MBs was found to fluctuate about its original diameter when exposed to ultrasound and higher intensity ultrasound was more effective in triggering the burst of CEHDA MBs. High ultrasound-triggered bubble disintegration effectiveness in a short period (first 5min) fits well with the requirement of short ultrasound exposure time for human brain. Moreover, a numerical model was also applied to investigate the stability of the fabricated MBs in the bloodstream. It was found that MB dissolution time increased with initial radius, decreased with initial surface tension and increased with initial shell resistance but it was barely affected by the average excessive bloodstream pressure.