内镜超声监测5-氟尿嘧啶温敏水凝胶治疗胰腺癌的实验研究

Monitoring 5-fluorouracil temperature-sensitive hydrogel interstitial chemotherapy for pancreatic cancer with endoscopic ultrasonography

目的利用内镜超声观察PLGA—PEG—PLGA-5-氟尿嘧啶温敏水凝胶对胰腺癌进行的治疗效果。方法（1）PLGA．PEG—PLGA．5-氟尿嘧啶温敏水凝胶的体外释放实验：测定不同时间点浸出液药物的浓度，计算释放量；（2）将胰腺癌细胞株SW1990皮下成瘤裸鼠50只随机分为5组，每组10只。A组瘤内注射PLGA-PEG—PLGA-5-氟尿嘧啶温敏水凝胶4mg／kg；B组瘤内注射PLGA—PEG-PL-GA-5．氟尿嘧啶温敏水凝胶1mg／kg；C组瘤体内注射5-氟尿嘧啶注射液4mg／kg；D组瘤体内注射瘤体内注射PLGA．PEG—PLGA基质4mg／kg；E组为空白对照组。于给药前、给药后3、7、10、14d应用内镜超声观察裸鼠肿瘤结节的生长及声像图，绘制肿瘤生长曲线；14d时处死动物，称瘤重，计算抑瘤率；行HE染色，观察不同组病理结果。结果（1）5-氟尿嘧啶温敏水凝胶药物释放率第1天为21．6％，第3天33．8％，第5天为44．3％，第8天为63．6％，第10天为76．3％，第14天为91．8％。（2）内镜超声测量不同时段瘤体大小，A组、B组瘤体与其他组相比明显缩小，差异具有统计学意义（P〈0．05）。超声内镜下图像特点与病理结果具相关性。结论PLGA—PEG-PLGA-5-氟尿嘧啶温敏水凝胶在14d内能在体外较稳定地持续释放，对人胰腺癌细胞株SW1990有持续抑制作用。该剂瘤内注射可明显抑制胰腺癌瘤裸鼠瘤体的生长，凝胶状制剂较液态制剂在瘤体内固定性好，内镜超声监测下5．氟尿嘧啶温敏水凝胶间质化疗胰腺癌的操作方便、安全；PLGA—PEG—PLGA-5-氟尿嘧啶温敏水凝胶制剂具有一定的潜在临床应用价值。

Objective To evaluate the therapeutic effect of PLGA-PEG-PLGA-5- fluorouracil temperature -sensitive hydrogel interstitial chemotherapy for pancreatic cancer by using endoscopic ultrasonogra- phy. Methods PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hydrogel in vitro release experiments were performed in the following procedures： determination of lixivium drug concentration and calculation of its emission . Fifty nude mice with the pancreatic cancer cell line SW1990 were randomly divided into 5 groups, 10 in each group. Group A was intratumorally injected with PLGA-PEG-PLGA-5-tluorouraeil temper- ature-sensitive hydrogel at 4mg/kg ; group B with PLGA-PEG-PLGA-5-fluorouracil temperature-sensitive hy- drogel at 1 mg/kg; Group C was intratumorally injected with 5-fluorouracil at 4 mg/kg ; Group D with PLGA- PEG-PLGA matrix at 4mg/kg ;and group E was the control group. Tumor growth and audio-visual images of the nude mice tumor nodules were observed before administration , and 3,7,10,14 days after. Tumor growth curve was also drawn. Animals were sacrificed at 14 days Tumors were weighed to calculate the inhibitory rate and stained for pathological study. Results 1,3,5,8,10,and 14-day release of 5-fluorouracil temperature-sensitive hydrogel were 21.6% , 33.8 % , 44.3% , 63.6% , 76.3% and 91.8% . Tumor sizes of group A and group B were significantly different from those of other groups （ P 〈0. 05 ）. Ultrasound endoscopic image characteristics were correlated with pathological findings. Conclusion PLGA-PEG-PLGA-5- fluorouracil temperature-sensitive hydrogel is able to release for 14 days in vitro , which constantly inhibits human pancreatic cancer cell line SW1990 . lntratumoral injection of the agent can significantly inhibit the growth of pancreatic cancer of nude mice . Additionally, gelatinous preparations fixes better than liquid and is of clinical value. Therefore, monitoring temperature-sensitive 5-fluorouracil hydrogel interstitial chemotherapy for pancreatic cancer with endoscopic ultrasound is convenient and safe .