壳聚糖-蒙脱土插层复合材料制备甲氨蝶呤缓释微球及其体外释放的研究  

Preparation of Methotrexate Sustained-Release Microspheres

作　　者：张丽娜 张倩 孙珊珊[2] 丁林[2] 王慧云[2] 全先高[2] ZHANG Li-na;ZHANG Qian;SUN Shan-shan;DING Lin;WANG Hui-yun;QUAN Xian-gao(School of Medicine and Life Science, University of Jinan , Jinan 250022, China;School of Pharmaceutical Science, Jining Medical University, Rizhao 276826, China)

机构地区：[1]济南大学医学与生命科学学院,济南250022 [2]济宁医学院药学院,山东日照276826

出　　处：《中国药学杂志》2017年第24期2172-2178,共7页Chinese Pharmaceutical Journal

基　　金：济宁医学院科研项目资助(JY2013KJ022);济宁医学院科研项目资助(JY2013KJ006);济宁医学院科研项目资助(JY2013KJ010)

摘　　要：目的制备新型甲氨蝶呤(MTX)缓释微球,并研究其体外释放性能。方法以蒙脱土(MMT)、壳聚糖(CS)为原料,采用原位插层法制得壳聚糖插层蒙脱土(CS-MMT),并以其为原料,采用乳化交联法制得载甲氨蝶呤的新型药物缓释体系,采用紫外可见分光光度计(UV-spectrophotometer)、傅立叶红外变换光谱仪(FT-IR)、马尔文激光粒度仪、电光显微镜表征载药微球的结构、性能及形态;以载药量和包封率为评价指标,考察了甲氨蝶呤的用量,油水比,乳化剂的用量,交联剂的用量等因素对载药微球载药量和包封率的影响;通过体外释放实验探讨了载药微球在不同模拟释放液中的释药规律。结果所得微球粒径分布较均匀,球形度好;在水油比为1∶5,戊二醛的用量为6%(水相),乳化剂用量为7%(油相),CS-MMT/CS为1∶4,MTX/CS为1∶3时制备的微球载药量与包封率最高。最优工艺制得的载药微球平均粒径为557.4 nm,载药量为31.6%,Zeta电位20.8 m V。体外释放实验表明,该缓释体系更倾向于在pH较低的盐酸溶液中释放,具有一定的pH敏感性。结论 CS-MMT可用作缓释辅料;CS-MMT微球是一种良好的药物缓释载体,且具有pH敏感性。OBJECTIVE To prepare a novel methotrexate sustained-release microspheres system, and study its in vitro re- lease properties. METHODS The CS-montmorillonite （CS-MMT） intercalative composites were prepared by using chitosan and montmorillonite. The novel drug sustained-release system was prepared with CS-MMT as the carrier material and methotrexate as the model drug. The microspheres were characterized by Fourier transform infrared spectrometer （FTIR） , electric microscope, UV-spectrophotometer （UV） , as well as Malvernlaser particle size analyzer. The influences of the amount of composite materi- als, dosage of emulsifiers, ratio of oil/water and dosage of crosslinking agent on the drug loading and entrapment rate of micro- spheres were investigated. And in vitro release experiment was used to study the drug release properties of the microspheres. RE- SULTS The shape and size of the microspheres were uniform. The drug loading, average particle size and Zeta potential were 31.6% , 557.4 nm and 20.8 mV respectively under the optimal conditions, ie, ratio of water/oil of 1 ： 5, amount of glutaralde- hyde（ aqueous phase） of 6% , dosage of emulsifiers （ oil phase） of 7% , CS-MMT/CS ratio of 1 ： 4, and MTX/CS ratio of 1 ： 3. Methotrexate sustained-release system was pH-sensitive and tended to show a larger release percentage in hydrochloric acid solu- tion. CONCLUSION CS-MMT can be used as a slow-release excipient. CS-MMT microspheres are good controlled-release carrier for drugs, with pH sensitivity.

关 键 词：蒙脱土 壳聚糖 甲氨蝶呤 微球 缓释 

分 类 号：R944[医药卫生—药剂学]