The Preparation Of A Magnetic Targeted Ultrasound Contrast Agent And Performance Study

Ultrasound-diagnosis has a wide application due to its non-invasiveness, cost effectiveness,and diagnostic significance. Ultrasound contrast agents （UCAs） have been attracted muchattention in recent years because they play a vital role in ultrasound-imaging, and bothtargeted-imaing and targeted-drug delivery make progress. Herein, PEG-based microbubbles andST68micbubbles were synthesized, and the ST68micbubbles were supported with magnetiteFe₃O₄nanoparticles, which were used as drug carrier. Magnetic properties andsonication-triggered drug release capacity have been particularly studied.The Fe₃O₄particles were prepared by co-precipitation technique, and were also modifiedusing sodium citrate. The structure, morphology and the surface functional of the UCAs groupwere characterized by means of XRD, IR, SEM and TEM. The SEM results show that theparticle size was from4nm to10nm, and the reunion phenomenon is not obviously observed.The synthesized Fe₃O₄nanoparticles exhibit excellent properties of superparamagnetism andbiocompatibility. So they can be used as targeted magnetic materials supported on the surface ofmicrobubbles.Two kinds of micro-bubble agents based on high polymer and surfactant were prepared byultrasonic cavitation method. The Laser particle size analyzer was used to analysis the particlesize distribution of micro-bubble agents. The results show that the particle size distribution isnarrow, and a large number of particles are less than8μm in size. Therefore, these micro-bubbleagents can meet the demand for circulation within human body. The morphology ofmicrobubbles was characterized by means of the optical microscope and SEM. The resultssuggest that microbubbles display uniform hollow ball. They can exist for a long time at4℃.ST68microbubbles are more stable and smaller in size than PEG microbubbles. The particle sizeof ST68and PEG microbubbles are about2.5μm and6.2μm, respectively. Therefore, ST68microbubbles were used as drug carrier to surface modification and drug transport.The Fe₃O₄nano-particles were assembled to the surface of ST68microbubble. Magnetismresponse of the microbubbles assembled Fe₃O₄nanoparticles was studied. The Norfloxacin waspackaged in microbubbles. Slow-release effect of drug was also studied. Controlled-release ofthe Norfloxacin from the microbubbles occurred in simulated human body fluid environment invitro. The drug-release and controlled release performance was estimated by real timemeasurement of Norfloxacin concentration using the ultraviolet spectrophotometry apparatus. The results show that the microbubbles have very good slow-release performance in vitro. Sothey can be used as drug or gene carrier to transport and designated control release.So they can be used as designated controlled release drug or gene delivery carrier. Theresults indicate that the contrast agents have very good targeted performance in vitro, and theycan provide images of particular area in the presence of an external magnetic field. Meanwhile,the microbubbles may break up under high power ultrasonic circumstance so that the internaldrugs can completely to be released.In the animal’s living experiments, rabbits were divided into two experimental groups forcontrast study. One group was fed with high fat egg yolk, and the other group was provided withnormal forage in the same conditions. The abdominal aorta imaging of the rabbits given high fatcan achieve accurate diagnosis of the fatty plaques in the blood vessels after microbubblescontrast agents were loaded magnetic targeted drug. Under the guidance of an external magneticfield, they can stay in the lesion site for a longer time, and the site-specific controlled release ofthe drug from the microbubbles can be triggered by focused ultrasound. The results indicate thatmicrobubbles contrast agents loaded magnetic targeted drug may favor early diagnosis of thedisease in vivo experiments, and diagnosis and treatment can be achieved simultaneously withassistance of them.