Experimental Research Of PLGA Microcapsules With Liquid Fluorocarbon Enhancing High Intensity Focused Ultrasound Energy Deposition

PART I PREPARATION OF PLGA MICROPARTICLESWITH LIQUID PERFLUOROCARBONS AND IN VITROEXPERIMENTObjective: To prepare a new type of ultrasound contrast agents-PLGAmicrocapsules of liquid perfluorocarbons, to research the conditions ofliquid-gas phase transition and effects on enhancing ultrasound and CTimaging in vitro.Methods: PLGA microcapsules of liquid perfluorocarbons werefabricated using an emulsion solvent-evaporation process,The morphologyand distribution were observed with optical and scanning electronmicroscope. The size and electric potential were obtained by using laser lightscattering analyzer. The conditions of liquid-gas phase transition wereresearched by using optical microscope and ultrasound imaging. Theenhancement effect in vitro was observed with CT imaging.Results: The PLGA microcapsules could be obtained with perfluorooctyl bromide (PFOB), perfluorohexane(PFH) respectively。Theaverage size of PLGA microcapsules with perfluorohexane (PFH/PLGA)increased with temperature and the number of PFH-PLGA microcapsulesdecreased with temperature after being heated up to70℃, but for PLGAmicrocapsules with perfluorooctyl bromide (PFOB/PLGA) there were nosignificant changes in morphological and acoustic after being graduallyheated up to80℃.In vitro CT imaging, the average CT value ofPFOB/PLGA microspheres group was significantly higher than that in othergroups, the difference was statistically significant (P <0.05).Conclusion: The liquid fluorocarbon PLGA microspheres could beused as a novel contrast agent due to its small particle size, good stability andbeing liquid-gas phase transition PART II EXPERIMENTAL STUDY OF PLGAMICROCAPSULES WITH LIQUID FLUOROCARBONENHANCING HIGH INTENSITY FOCUSEDULTRASOUND ABLATION OF NORMAL LIVERObjective: To study the optimal power of self-made polymericmicrocapsules with liquid fluorocarbon enhancing high intensity focused ultrasound (HIFU) ablation of normal bovine in vitro and the treatmentefficacy of HIFU ablation of normal rabbit liver in vivoMethods: The experiment was divided into two parts: the first part wasHIFU ablation of bovine in vitro: The bovine was injected different drugsbefore HIFU ablation to find the optimal power and treatment time. It wasdivided into four groups:①HIFU+NACL group,②HIFU+PLGA group,③HIFU+PFH group,④HIFU+PFH/PLGA group; The second part wasHIFU ablation of normal rabbit liver. Similarly, It was also divided into fourgroups as above. Each group was underwent HIFU ablation with sameparameters after ear vein injection of drug. Then observed and compared theultrasonographic change and its value, and the actual situation of liverdamage in target areas of each group before and after the ablation area.Results: In experiments of vitro bovine, gray scale changes andcoagulation necrosis could be seen in the liver in group2、3、4with HIFUpower of150W and treatment time of2s. In experiment of normal rabbitliver, the average gray-scale of group3and4were larger than that in group1and2, the difference was statistically significant (P <0.001), and its graychange area gradually reduced with time elapsed. While there was nostatistically significant difference between groups3and4(P>0.05); Inpathological specimens, there was no significant liver damage in groups1and2, there was hemorrhagic necrosis and white coagulation necrosis ingroup3and4. Conclusion: The polymeric microcapsules with liquid fluorocarboncan effectively enhance the efficacy of HIFU ablation and be used as a goodsynergist for HIFU.