Research On High Molecular Polymer Ultrasound Contrast Agent For Drug Delivery

Cancer is a main disease to threat the health of human being. Chemical therapy is an important method to treat it comparing with operation and radial therapy. Most anticancer drugs are cytotoxinic with greater toxicity. Targeted drug delivery system can direct the drug to the treatment site, improve the drug concentration, reduce the drug consumption and adverse reactions, and improve drug safety, efficacy and patient compliance. So currently, it is the focus of anti-tumor therapy research. A recent study showed that "cavitation effects" and "sound-effect" that are generated in the ultrasonic cavitation process can achieve in vivo drug release positioning and improve the therapeutic effect. Ultrasound contrast agent (UCA) as a novel in vivo targeted drug delivery system receives widespread attention.PLGA, a novel artificial and biodegradable high molecular polymer-polylactic-co-glycolic acid, was employed to fabricate the ultrasound contrast agent with Mytomycin(MMC) and C₃F₈ inside by a double emulsion method and lyophilization method. We used light microscope and scan electron microscope to study the shape and surface morphology of the MMC-PLGA ultrasound contrast agent. The experiment in vitro was employed to study the effects of MMC-PLGA ultrasound contrast agent on the enhancement of ultrasound imaging. The experiment of ultrasound irradiation was employed to study the drug controlled-release. The following are the research results:1. The preparation and characterization of MMC-PLGA ultrasoundcontrast agentMMC-PLGA ultrasound contrast agent was produced with a uniform size of 0.5～5μm through optimized experiment. Contrast agent lyophilized powder has a good dispersion when dissolved. Laser particle size analyzer was used to detect the size distribution. The results showed that the average particle size is 2.86μm, and the size of the microspheres has a relationship with the installation of heterogeneous machines in the preparation. The most loading capacity of the drug microbubbles were 3.39%, and the encapsulation rate was 32.2%. 2. In-vitro autoradiography and irradiation experimentsThe experiment showed that MMC-PLGA ultrasound contrast agent had a good in-vitro auto -radiography effect. The amount of microbubble drag release could reach 90.95 % with 1.0W/cm² ultrasonic irradiation, which was much higher than 31.38%—the amount of microbubbles initial in vitro release—that without any ultrasonic irradiation. Ultrasonic irradiation had an evident effect in controlled drag release.MMC-PLGA ultrasound contrast agent had a good autoradiography effect, and meanwhile realized the drag controlled release. The study laid a foundation for the use of ultrasonic and ultrasound contrast agent for in vivo drag delivery.