胸腺五肽pH-敏感壳聚糖纳米粒的制备、体外释放及生物活性  

Study on Preparation Release in Vitro and Biological Activity of Thymopentin-Loaded pH-Sensitive Chitosan Nanoparticles for Oral Administration

作　　者：郑爱萍[1] 王奎书[2] 郝睿[2] 李明光[1] 王坚成[1] 张强[1] 

机构地区：[1]北京大学药学院药剂教研室,北京100083 [2]河北省邯郸市第一医院,河北邯郸056002

出　　处：《中国药学杂志》2007年第9期679-685,共7页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30430760)

摘　　要：目的为了提高胸腺五肽口服的稳定性及生物利用度,制备胸腺五肽pH-敏感壳聚糖纳米粒并考察其理化性质、体外释放及生物活性。方法采用离子胶凝法制备胸腺五肽壳聚糖纳米粒并用Eudragit S100包衣制备pH-敏感纳米粒;透射电镜和环境扫描电镜观察纳米粒形态;粒度及表面电位分析仪测量纳米粒的粒径及Zeta电位;超速离心法测定载药纳米粒的包封率;动态透析法研究载药纳米粒的体外释放特性;模拟人工消化液考察纳米粒中胸腺五肽的生物稳定性;淋巴细胞增殖反应评价制剂的生物活性。结果pH-敏感胸腺五肽壳聚糖纳米粒的平均粒径为(175.6±17)nm,Zeta电位为(28.44±0.5)mV,包封率为(76.70±2.6)%。胸腺五肽pH-敏感壳聚糖纳米粒具有良好的pH依赖性:在0.1 mol.L-1HCl溶液中累积释放24.65%,在pH5.0 PBS溶液中累积释放41.01%,在pH7.4 PBS溶液中累积释放81.44%。pH敏感壳聚糖纳米粒制剂中的胸腺五肽在人工胃液中稳定,在人工肠液中半衰期为15 min。淋巴细胞体外转化实验表明,胸腺五肽pH-敏感壳聚糖纳米粒保留了TP5的生物活性并且具有浓度依赖性。结论pH-敏感壳聚糖纳米粒可能是口服胸腺五肽的良好载体。OBJECTIVE To prepare pH-sensitive chitosan nanoparticles, and investigate their physicochemical characteristics, drug release in vitro and biological activity in order to improve the stability and the oral bioavailability of thymopentin evaluated. METHODS Thymopentin-loaded chitosan nanoparticles were achieved by ionic gelation methods, which were coated by Eudragit S100 in order to obtain pH-sensitive nanoparticles. Nanoparticle morphology was examined by transmission electron microscope and environment scan electron microscope. Nanoparticle size and Zeta potential were measured by zetasizer nano analyser. The entrapment efficiency of TPS-loaded nanoparticles was surveyed by supercentrifugate. Dynamic dialysis technique was used to determine the releasing characteristic of nanoparticles in vitro. The biological stability of TPS-loaded nanoparticles was explored in artificial digestive juice. Biological activity was assayed by lymphocyte transformation test. RESULTS The average sizes of pH-sensitive chitosan nanoparticles were （ 175.6 ± 17 ） nm, and the Zeta potential of the nanoparticles was （ 28.44 ± 0. 5 ） mV. The entrapment efficiency of the nanoparticles was （76. 70 ± 2. 6）%. The release behavior of the pH-sensitive chitosan nanoparticles was carried in three kinds of release medium： 0. 1 mol · L^-1 HCl,pH 5.0 PBS and pH 7.4 PBS,and the accumulated release percentages of thymopentin from these medium were 24.65% ,41.01% and 81, 44% respectively. TP5 loaded in pH-sensitive chitosan nanoparticles had good biological stability in artifical gastric fluid and its halflife in artifical intestinal fluid was 15 min, Lymphocyte transformation test verified that the pH-sensitive chitosan nanoparticles had the same biological activity as TP5 did and were concerntration-dependented, CONCLUSION These results indicate pH-sensitive chitosan nanoparticles may be used as the vector in oral drug delivery system for TP5.

关 键 词：胸腺五肽 壳聚糖 纳米粒 

分 类 号：R943[医药卫生—药剂学]