中文摘要：

目的全面考察实验室前期自行合成的mPEG—PCL两嵌段高分子，并采用双乳化法将其用于负载顺铂，评价该纳米微球的体内外抗肿瘤活性。方法通过开环聚合法，制备mPEG—PCL两嵌段聚合物以及末端带有羟基的PCL作为载体，采用优化的w／o／w双乳化扩散／挥发法，制备负载顺铂的纳米微球。采用MTT法，评价该纳米微球在体外对于消化系肿瘤细胞株BGC823、HepG2、H22的抗肿瘤活性，并与顺铂裸药相比较。在BGC823及102细胞株上验证空白微球的毒性。在ICR小鼠皮下接种H22肿瘤模型，采用瘤体内注射，验证纳米微球的抗肿瘤活性和副作用，并与顺铂裸药比较。结果通过开环聚合法合成mPEG—PCL两嵌段聚合物以及末端带有羟基的PCL，测定分子量和设计分子量相近。载药微球粒径（370.3±2．5）nm。顺铂的载药效率为77．4％，载药量为4．72％。体外释放实验显示，载药微球具有缓释特征。载药微球对于体外培养的肿瘤细胞系的抗肿瘤和顺铂裸药相似。空白微球对于肿瘤细胞BGC823及人肝细胞株L02均无明显毒性。在体内实验中，载药微球对于肿瘤生长的抑制作用优于顺铂裸药，且呈现更好的剂量依赖性，当给药剂量从2．5mg／kg增加到5mg／kg时，抑瘤率提高，而顺铂裸药的抑瘤率并不因剂量的增加而提高。当顺铂裸药的给药剂量从2．5mg／kg增加到5mg／kg时，小鼠的体重增长明显减缓，而顺铂微球的剂量增加时，小鼠的体重变化并不受到明显影响。结论采用mPEG—PCL为载体，双乳化法合成的顺铂纳米微球，具有稳定及缓释的性质，在体外实验中，其抗肿瘤活性略低于裸药，和纳米微球的缓释特性有关。在体内实验中，载药微球的抗肿瘤活性优于顺铂裸药，且副作用小，因此动物能够耐受更大给药剂量。空白微球在体内外实验中均无明显毒性，说明载体应用安全?

英文摘要：

Objective To prepare elsplatin-loaded nanoparticles with bi-bloek eopolymer mPEG-PCL and PCL, and evaluate their antitumor effect in vitro and in vivo. Methods mPEG-PCL and HO-PCL were synthesized by ring-opening polymerization method and the nanoperticles were prepared by developed w/o/w double emulsion method. The in vitro cytotoxieity of cisplatin-loaded nanoparticles and toxicity of the blank nanoparticles were evaluated by MTT assay. We assess the antitumor efficacy of nanoparticles in vivo and free cisplatin on mice implanted subcutaneously with H22 cells. The antitumor effect of the two formulations was determined by tumor volume measurement, and the toxicity was studied by body weight measurement. Results mPEG-PCL and PCL are synthesized with desired molecular weight. The diameter of cisplatin-loaded nanoparticles is （370.3 ± 2.5） nm. The encapsulation-efficiency and drug loading content are 77.4% and 4, 72% respectively. In vitro the release presents a sustain-release pattern. The nanoparticles exhibites similar cytotoxicity compared to free cisplatin while the blank nanoparticles are non-toxic to the cell line. According to in vivo studies in vivo, the cisplatin-loaded nanoperticles showed better antitumor effect than free cisplatin at the same dosage. As to the side effect, mice in the group of nanoparticles in vitro showed milder body loss. Conclusions the nanoparticles synthesized with mPEG-PCL and PCL was characterized by sustained-relaease. The antitumor effect of nanoparticles in vitro was similar to free cisplatin. According to study in vivo, the cisplatin-loaded nanoperticles showed better antitumor effect than free cisplatin at the same dosage. As to the side effect, mice in the group of nanoparticles showed milder body loss. The above findings indicate the potential of this nanoparticles as carrier for cisplatin.