【作者】 常江；

【导师】 崔兰；

【作者基本信息】 天津大学 ， 材料学， 2003， 硕士

【摘要】 卡氮芥是一种有效治疗恶性神经胶质瘤的药物，临床疗效显著，是目前脑瘤治疗的首选药物。但半衰期短，难溶于水，毒副作用大。为克服上述缺点，本文采用溶剂挥发法制备了抗癌药物BCNU的聚乳酸微球。用扫描电子显微镜（SEM），光学显微镜观察其表面形态，显色法测定微球载药率，考察了不同制备条件对微球的粒径和形态，载药率，包封率等性能的影响。可观察到所制备载药微球表面光滑圆整，粒径分布均匀。结合SEM分析，微球粒径受油相分散方式和聚乳酸分子量的影响显著。载药率可达15％左右，药物包封率可达40％左右。用差热扫描分析（DSC）对载药微球中药物分布状态及稳定性进行测定：BCNU在PLA基质中以分子状态存在，其药物稳定性有所下降。载药微球体外释放试验显示聚乳酸分子量、药物含量、微球粒径对PLA-BCNU微球释放有不同程度的影响。微球释药时间长，可持续释放70天左右，释药速率较稳定，符合Higuchi时间平方根模型。提高微球表面光滑度可适当减小药物突释程度和时间。SEM观察水解后聚乳酸微球，其骨架仍然存在，但球形较不规则，表面出现一些凹凸不平，这与聚乳酸微球自身的降解和药物的溶出有关。并对PLA和PLA/PEG共混两种载药膜片的释放、降解行为作出比较。PLA在加入PEG后，其药物释放速率和本身降解速率明显加快，可进一步改善PLA释药特性。更多还原

【Abstract】 BCNU, relatively high lipid solubility and low molecular weight, is widely used for the treatment of malignant gliomas. However, BCNU is limited by its systemic toxicity and characteristic, such as its water-insolution and short half life. In order to solve these problems, the following work has been done in this dissertation.PLA-BCNU microspheres(MPs) were prepared by Solvent evaporation process via using PLA as the polymer matrix. Through SEM(Scanning electronic microscope) micrograph, the microspheres sizes and standard deviation were effected by molecular weight and oil-phase distribution models. Smooth surface without cavities or crystal of the drug could be get in this dissertation. Colorimetric method was used to determinate drug loaded ratio and drug encapsulation efficiency of MPs, and they could reach 15% and 40%, respectively. BCNU dispersion and stability in the MPs was studied by DSC(Differential scanning calorimetry analyses).The in vitro release experiments studied the effects of molecular weight of PLA, drug content in MPs and MPs sizes on release behavior of microspheres. The release BCNU microspheres was slow(>70day) and stable, and could be described as square root-time process. Improve the surfaces of MPs could weaken their degree of burst release. Some degradation of MPs after releasing for 1 month could be seen by SEM. The basic sphericity was remained but with some cavities which were the channels for BCNU when delivered into the environment.Addition of PEG to PLA film can improve release behavior of PLA-BCNU carrier by increasing the speed of drug release.更多还原