Study On Treatment Of Rabbit Liver Tumor Using Drug-loaded Microbubbles And Low Intensity Focused Ultrasound Targeted Destruction

PART I PRELIMINARY STUDY ON TARGETEDMICROBUBBLES DESTRUCTION USING LOW INTENSITYFOCUSED ULTRASOUNObjective1To explore the destruction range and space distribution ofmicrobubbles using low power focused ultrasound (LIFU).2To observe the targeted destruction using paclitaxel-carryingliposome microbubble（PLM）and LIFU in the liver of rabbit.Methods1MB were prepared by mechanical shaking，then added it to a certainamount of normal saline, prepared bladders containing microbubbles.Iirradiated the bladder containing lipid microbubbles with the four differentintensities of LIFU（0.3W/cm~2，0.6W/cm~2，0.9W/cm~2，1.2W/cm~2）, observed and recorded the destruction ranges and spatial distributionshapes of the microbubbles in the bladder from different facets with Philipsiu22.2PLM were prepared by mechanical shaking.10rabbits wererandomly divided into focused ultrasound group (A) and focusedultrasound group (B)，each group of5.After being injected PLM, Group A,B were irradiated respectively with LIFU and non-focused ultrasound at theliver for2min. Then sacrificed the rabbits and harvested the liver tissues atthe center of the focal region and at different distances from the center tomeasure paclitaxel concentration with high-performance liquidchromatography（HPLC）.Results1LIFU could destructe microbubbles in a specific position，thedestruction ranges were limited，the shapes were rule-olive，and the rangesincreased with the increase of intensify.2In Group A，paclitaxel concentration at the center was the highest,and drug concentration decreased with the increase of distance from thecenter（F=201.81，P<0.05）；There were no significant differences of drugconcentration at different distances in Group B（F=1.36，P>0.05）；Thepaclitaxel concentration at the center in Group A was higher than that ofGroup B（t=5.28，P<0.05）. Conclusions1LIFU could achieve targeted microbubbles destruction, and itsfocused sites and microbubble destruction ranges are adjustable. LIFU isexpected to become specialized ultrasound irradiation system for targetingblasting microbubble.2LIFU is able to achieve positioning controlled release of the drug invivo, which provided a foundation for the further study on precisepositioning release of drugs for targeted drug therapy of tumor. PART II STUDY ON TREATMENT OF RABBIT VX2LIVER TUMOR USING PLM AND LIFUTARGETED DESTRUCTIONObjective To investigate the therapeutic effect of rabbit VX2tumorusing PLM and LIFU targeted destruction.Methods PLM were prepared by mechanical shaking,and to detectthe characteristics of PLM. Built rabbit VX2tumor models with tumormass embedding, and finally20tumor-bearing rabbits into the experiment. 20rabbits were randomly divided into4groups: Control (A), PLM (B),Non-focused ultrasound+PLM (C),Focused ultrasound+PLM(D). Therabbits in Group A were injected NS.Group B,C,D were injected PLM, thenGroup A was not irradiated, Group C and D were irradiated withnon-focused ultrasound and LIFU at the tumor site for2min,twice a week,a total of4times. Observed the volumes of tumors before and aftertreatment with ultrasound, calculated and compared the tumor volume (TV)and tumor inhibition rate(TIR).After all treatments, rabbits were sacrificedand the tumors were harvested to observe the expression of PCNA withimmunohistochemistry, detecte the apoptosis with TUNEL.Results In Group D, the growth speed of tumor was the slowest，the TIR and AI were significantly higher than the other groups (P <0.05),the GI was significantly lower than the other groups (P <0.05), the effectof treatment was best.Conclusions Drugs can be targeted-released using LIFU anddrug-loaded microbubbles. The targeting of LIFU is improvedfurther,which can improve the targeted treatment of diseases significantly.