【作者】 林锦超；

【导师】 张俊卿；

【作者基本信息】 福建医科大学 ， 外科学， 2009， 硕士

【摘要】 目的:优化工艺制备吐温80和(或)PEG20000双重修饰的聚氰基丙烯酸正丁酯纳米载体,进一步制备包载福莫司汀、替莫唑胺的聚氰基丙烯酸正丁酯纳米粒。方法:(1)选择α-氰基丙烯酸正丁酯为载体材料,吐温80和(或)PEG20000为表面修饰材料,用乳液聚合法制备双重修饰的聚氰基丙烯酸正丁酯纳米载体。在单因素试验基础上,进行均匀设计,并优化制备工艺。(2)进一步制备包载福莫司汀、替莫唑胺的聚氰基丙烯酸正丁酯纳米粒,通过考察粒径大小和包封率两个指标,优化制备工艺。结果:(1)优化条件下制备的双重修饰的聚氰基丙烯酸正丁酯纳米载体(PBCA-NP)为乳白色胶体溶液,透射电镜观察纳米载体呈圆形,无粘连。粒度分析仪测定平均粒径约137.7nm,粒子分散度(PDI)为0.190。(2)优化条件下制备的包载福莫司汀的聚氰基丙烯酸正丁酯纳米粒(FCNU-PBCA-NP)为乳白色胶体溶液,透射电镜观察纳米粒呈圆形,无粘连。粒度分析仪测定平均粒径为(124.6±5.2)nm,粒子分散度(PDI)范围为0.07-0.16,平均包封率ER为(64.12±2.36)%。(3)优化条件下制备的包载替莫唑胺的聚氰基丙烯酸正丁酯纳米粒(TMZ-PBCA-NP)为乳白色胶体溶液,透射电镜观察纳米载体呈圆形,无粘连。粒度分析仪测定纳米粒平均粒径约125.1nm,粒子分散度(PDI)为0.098,替莫唑胺包封率(ER)约83.02%。结论:首次以α-氰基丙烯酸正丁酯为载体材料,吐温80和(或)PEG20000为表面修饰材料,用乳液聚合法制备双重修饰的聚氰基丙烯酸正丁酯纳米载体,并经优化筛选出最佳制备工艺,并进一步成功制备包载福莫司汀、替莫唑胺的聚氰基丙烯酸正丁酯纳米粒,对拓展福莫司汀、替莫唑胺临床给药新剂型提供一定的参考,并对进一步研究其缓释性和脑靶向性奠定基础。目前国内外未见报道。更多还原

【Abstract】 Objective:To prepare polybutylcyanoacrylate(PBCA) nanocarriers with optimized process,double-located with Tween80 and(or) polyethylene glycol(PEG)20000,to further prepare fotemustine polybutylcyanoacrylate nanoparticles(FCNU-PBCA-NP) and temozolomide polybutylcyanoacrylate nanoparticles(TMZ-PBCA-NP).Method:(1)Double-coated PBCA nanocarries was prepared by emulsion polymerization method with butylα-cyanoacrylate(BCA) as carrier materials, Tween80 and(or) PEG20000 as surfactants,and the procedure was optimized by both single factor test and uniform design test.(2) To further prepare fotemustine polybutylcyanoacrylate nanoparticles(FCNU-PBCA-NP) and temozolomide polybutylcyanoacrylate nanoparticles(TMZ-PBCA-NP),and optimize the preparing technology according to the particle size and the embedding ration(ER).Results:(1) The solution of double-coated PBAC-NP under optimum conditions was milk-white colloidal solution and the nanocarriers were circular and non-adhesion through transmission electronic microscopy.The average particle size was about 137.7nm and particle density index(PDI)was about 0.190.(2) The solution of fotemustine polybutylcyanoacrylate nanoparticles(FCNU-PBCA-NP) under optimum conditions was milk-white colloidal solution and the nanocarriers were circular and non-adhesion through transmission electronic microscopy.The average particle size was about(124.6±5.2)nm and particle density index(PDI) was about 0.07～0.16.the average embedding ration(ER) was about(64.12±2.36)%.(3)The solution of temozolomide polybutylcyanoacrylate nanoparticles(TMZ-PBCA-NP) under optimum conditions was milk-white colloidal solution and the nanocarriers were circular and non-adhesion through transmission electronic microscopy.The average particle size was about 125.1nm and particle density index(PDI) was about 0.098.the average embedding ration(ER) was about 83.02%.Conclusion:Double-coated PBCA nanocarries was prepared by emulsion polymerization method with butylα-cyanoacrylate(BCA) as carrier materials, Tween80 and(or) PEG20000 as surfactants for the first time,and the procedure was optimized by uniform design test.fotemustine polybutylcyanoacrylate nanoparticles (FCNU-PBCA-NP) and temozolomide polybutylcyanoacrylate nanoparticles (TMZ-PBCA-NP) were successfully prepared On this basis.They have provided a new direction for fotemutine and temozolomide dosage forms,and laid the foundation for Research for Sustained release and targeting of brain.They have not been reported at home and abroad at present.更多还原