紫杉醇原位凝胶的制备及其抗肿瘤骨转移的作用研究

Study on Preparation of paclitaxel in situ gel and its effect on Anti-bone metastasis of Tumor

关键词:  紫杉醇  原位凝胶  肿瘤骨转移

Key words:  paclitaxel  in situ gel  bone metastasis of tumor

摘要:

目的 制备紫杉醇原位凝胶，考察其理化性质及对体内肿瘤骨转移的作用。方法 冷溶法制备紫杉醇原位凝胶，考察其稳定性及体外释放特性；建立裸鼠乳腺癌骨转移MRMT-1细胞模型，通过瘤内局部给药，研究其体内抗肿瘤骨转移的作用。结果 制得的紫杉醇原位凝胶的胶凝温度为32.3℃，其体外释药曲线为Q=2.557 9 t +28.067，r=0.999 5，符合零级动力学方程。动物试验结果表明，紫杉醇原位凝胶给药后能有效降低裸鼠肿瘤体积，其抑制作用与给药剂量呈正相关。X射线检查显示，空白凝胶组裸鼠骨质受损严重，紫杉醇原位凝胶给药后，裸鼠骨受损情况显著改善；与空白凝胶组相比，紫杉醇原位凝胶高浓度组骨密度显著上升(P<0.05)。结论 制备的紫杉醇原位凝胶体外释放良好，能够显著抑制乳腺肿瘤骨转移，改善肿瘤引起的骨质受损。

Abstract:

OBJECTIVE To prepare paclitaxel in situ gel and to investigate its physical and chemical properties and effect on bone metastasis of tumor in vivo. Methods Paclitaxel in situ gel was prepared by cold solution method, and its stability and release characteristics in vitro were investigated. The MRMT-1 cell model of breast cancer bone metastasis in nude mice was established to study the effect of anti-bone metastasis of tumor of paclitaxel in situ gel in vivo by local administration in tumor. Results The gelation temperature of paclitaxel in situ gel was 32.3 ℃, and the drug release curve in vitro was Q=2.557 9t+ 28.067, r=0.999 5, which fit the zero-order kinetics equation. Animal experiment results showed that paclitaxel in situ gel could effectively reduce tumor volume in nude mice, the inhibitory effect was positively correlated with the dosage. X-ray examination showed that bone damage of nude nice was severe in the blank gel group, and bone damage of nude mice was significantly improved after of paclitaxel in situ gel administration. Compared with the blank gel group, bone density was also significantly increased in nude mice in the high concentration of paclitaxel in situ gel group(P<0.05). Conclusion The paclitaxel in situ gel prepared in this study has good release characteristics in vitro, and can significantly inhibit tumor bone metastasis and improve the bone damage caused by tumor.