Experimental Study On The New Vascular Embolic Agent Of Pol (N-isopropylacrylamide) Microgel

PART I:Preparation and physical characterization description of IB and doxorubicin loaded-IB (IBi-D)Objective: To prepare IB and drug loaded-IB (IBi-D) and describe its physical characterization.Materials and Methods:The poly-isopropyl acrylamide used as a substrate, methods for the preparation IB with improved precipitation polymerization and IBi-D with physically mixed.Results:The IB and IBi-D have a nice viscosity and flow characteristics, they can be used for2.7F microcatheter injection. The IB has an ability to load doxorubicin and release drug characteristics in vitro, which is stable and in144hours can release80%doxorubicin.Conclusion:Prepared using a modified process can obtain IB and IBi-D with good characteristics, viscosity liquidity and moderate, good performance of manipulated within the catheter, stability capability of drug load. IB can be used as a well antineoplastic drug carrier and a novel liquid embolization agent. PART II:An experimental study on the embolization of rabbit renal arteries with IB and doxorubicin loaded-IB (IBi-D)Objective: Feasibility study of IB for vascular thrombosis, controllability for use, biocompatibility and durability of vascular occlusion, investigate its long-term efficacy of embolization. IBi-D used to evaluate its drug characteristics.Materials and Methods:30right kidney embolism rabbits model used in this experiment, the right side of the renal artery was embolized with injection of IB or IBi-D. Review times were set at the point of1week,1month,2months and3months, angiography used to evaluate the recanalization and formation of new born collateral vessel and pathological examination to evaluate its durability of embolization. Then investigate its long-term efficacy of embolization and the Doxorubicin release characteristic of IBi-D.Results:Embolization of renal peripheral arteries achieved with IB injection into the renal artery, only mild inflammatory response was found and without foreign body granuloma formation or disruption of the vessel wall. In the follow-up period of three months, no recanalization and collateral circulation recanalization appeared in the angiography.Conclusion:Embolization renal artery with IB was effective, and IB has a feature of lower viscosity fast and temperature response and well thixotropic and biocompatibility. IB might be a suitable material for experimental study of intravascular embolization. PART HI:An comparative experimental study on the embolization of rabbit VX2liver tumors with doxorubicin loaded-IB (IBi-D)Objective:To observe the growth of rabbits hepatic VX2tumor of transcatheter arterial embolization using IB and doxorubicin loaded-IB (IBi-D), and investigate its antitumor efficacy.Materials and Methods:Forty rabbits liver VX2tumors model used and randomly divided into3groups of10each after diagnosed by MR. A3F catheter was inserted into the hepatic artery and procedure of interventional therapy was performed separately. Different agent was inserted the tumor artery:about0.4ml IBi-D in group A,0.4ml IB in group B,0.4ml DOX in group C and0.4ml physiological saline in group D, respectively. MR scans were preform in1day before and7days after the treatment. Tumor average volumes before (V1) treatment and volumes (V2) after treatment were measured, respectively. The tumor growth ratios (V2/V1) were calculated. Animals were sacrificed and hepatic tumor tissue was obtained for pathological examination at the end of study. Survival of the experimental animals was observed. Tumor volume, growth rates and necrotic rates were comprehensive evaluation with radiologic and pathologic methods.Results: IBi-D injected through the catheter into the target tumor area and embolized the tumor blood vessels and feeding arteries are available. There was no significant difference in the volume of tumors at1day before treatment (P<0.05, ANOVA). The mean tumor growth ratio was90.82%+19.34in group A,120.71%±33.24in group B,331.45%±32.54in group C and381.50%±33.17in group D, respectively. There was significant difference between each group (P<0.05, Bonferroni). Comparison with IBiD embolization group, activity tumor cells were observed in the junction of tumor and normal hepatic cells. Tumor necrosis broader and more completely in group A and B compare to the control groups (group C and D).Conclusion: Transcatheter arterial embolization using doxorubicin loaded-IB (IBi-D) resulted in significant inhibitory effect for tumor growth and metastasis, might be an effective tumor therapeutic material.