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目的 :制备同时荷载紫杉醇(paclitaxel,PTX)和顺铂(cisplatin,DDP)的水凝胶药物体系PDMP[polyethylene glycol-polycaprolactone-polyethylene plycol(PECE)/DDP+methoxypolyethylene glycols-polycaprolactone(MPEG-PCL)/PTX],探讨其在动物体内对宫颈癌的抗肿瘤作用,以及可能的作用机制。方法:通过固体分散法制备MPEG-PCL/PTX胶束,然后与PECE水凝胶和DDP溶液混合,合成PDMP凝胶药物。采用高效液相色谱法、激光粒径分析仪和流变仪检测PDMP凝胶药物的理化性质。建立宫颈癌He La细胞的裸鼠移植瘤模型,随机分为4组:对照组(0.9%氯化钠溶液)、单纯载体组(PECE+MPEG-PCL)、游离药物组(PTX+DDP)和PDMP凝胶药物组;每组12只。通过瘤内注射的方式进行给药后,观察各组荷瘤裸鼠的肿瘤生长情况;并在给药第10天时,每组处死6只裸鼠,取出肿瘤组织,采用免疫组织化学法检测肿瘤组织中Ki-67的表达水平,并采用FCM法检测肿瘤细胞的周期分布及凋亡情况。继续培养剩余的每组6只荷瘤裸鼠,观察其生存时间。结果:PDMP凝胶药物制备成功。与其他组相比,PDMP凝胶药物能明显抑制裸鼠体内肿瘤的生长(P值均<0.05),延长荷瘤裸鼠的生存时间(P值均<0.05);PDMP凝胶药物作用能明显降低肿瘤组织中Ki-67的阳性表达率(P值均<0.05),引起G1期细胞阻滞(P值均<0.05),同时提高肿瘤细胞的凋亡率(P值均<0.05)。结论 :PDMP凝胶药物可能是一种适合宫颈癌原位治疗的有效的用药体系。
OBJECTIVE: To prepare PDMP (polyethylene glycol-polycaprolactone-polyethylene plycol (PECE) / DDP + methoxypolyethylene glycols-polycaprolactone (MPEG-PCL) / PDMP) solution with simultaneous loading of paclitaxel (PTX) and cisplatin (DDP) PTX] to investigate its antitumor effect on cervical cancer in animals and its possible mechanism. Methods: MPEG-PCL / PTX micelles were prepared by solid dispersion method and then mixed with PECE hydrogel and DDP solution to synthesize PDMP gel. The physicochemical properties of PDMP gel were tested by high performance liquid chromatography, laser particle size analyzer and rheometer. Nude mice transplantation tumor model of cervical cancer He La cells was established and randomly divided into 4 groups: control group (0.9% sodium chloride solution), vehicle group (PECE + MPEG-PCL), free drug group (PTX + DDP) PDMP gel drug group; 12 in each group. After intratumoral injection, the tumor growth of nude mice in each group was observed. On the 10th day after administration, 6 nude mice were sacrificed in each group, and the tumor tissues were removed and detected by immunohistochemistry The expression of Ki-67 in the tissue was detected by FCM and the cell cycle distribution and apoptosis were detected by FCM. Continue to train the remaining 6 nude mice per group, to observe the survival time. Results: PDMP gel preparation was successful. Compared with other groups, PDMP gel drugs can significantly inhibit the growth of tumors in nude mice (all P <0.05), prolong the survival time of nude mice bearing tumors (all P <0.05), PDMP gels can obviously (P <0.05), which caused the cell arrest in G1 phase (all P <0.05) and the apoptosis rate of tumor cells (P <0.05). Conclusion: PDMP gel may be an effective drug delivery system for cervical cancer in situ.