Research Of Injection Of Doxorubicin-carrying Liquid-solid Phase Variant In Situ Gel For The Treatment Of Rabbit Residual VX2Liver Cancer After HIFU Irradition

Objectivs: To develop the doxorubicin-carring liquid-solid phasevariant in situ gel, learn the drug cumulative release curve and observe themorphology of phase variant of the in situ forming implant; To studytreatment effect of doxorubicin-carrying liquid-solid phase variant in situ gel forresidual rabbit VX2liver cancer after high intensity focused ultrasound treatmentby means of tumor size,the distribution of the gel in the tumor,tumorproliferation index and expression of related protein.Methods: The doxorubicin-carring liquid-solid phase variant in situgel was prepared with Polylactic-co-glycolic acid(PLGA), N-Methylpyrrolidone(NMP) and Doxorubicin(DOX),its drug release cumulativecurve and the morphology of phase variant of the in situ formingimplant(ISFI) were tested by high performance liquidchromatography(HPLC) and some ultrasound dynamic observation. Set uprabbit VX2liver tumor mode1.24rabbits which received HIFU non-complete ablation were randomly assigned to2groups, i.e. HIFU+DOX-ISFI group (useddoxorubicin-carrying liquid-solid phase variant in situ gel treatment after highintensity focused ultrasound treatment), HIFU+N-ISFI group (used drug-freeliquid-solid phase variant in situ gel treatment after high intensity focusedultrasound treatment). Tumor growth rates were compared. PCNA expressionwas detected by immunohistochemistry. The distribution of drug in cancer wasobserved with a fluorescent imager of frozen tissue samples. Western blot wasused to detecte the expression of Bcl-2and Bax.Results: The drug release cumulative curve indicated that total drugrelease rate is (43.13±5.91)%, ultrasound dynamic observationdisplayed the morphology of phase variant of the in situ forming implant.Tumor growth rate of HIFU+DOX-ISFI group was obviously lower thanthe HIFU+N-ISFI group(P<0.05). Proliferating index of HIFU+DOX-ISFI group was dramatically lower than the HIFU+N-ISFIgroup(P<0.05). Fluorescence imaging showed the drugs from the injectioncenter around to a ladder shape distribution. The protein expression ofBcl-2of the HIFU+DOX-ISFI group was decreasedsignificantly(P<0.05),the result of the protein expression of Bax wasreversed.Conclusions: Doxorubicin-carrying liquid-solid phase variant in-situ gelcan effectively treatment the residual rabbit VX2liver cancer after HIFU treatment as to provide reference for the treatment of liver cancer.