低分子肝素pH敏感巯基壳聚糖纳米粒的制备及体外黏膜透过性评价  

Preparation and In vitro Mucosal Penetration Evaluation of pH-Sensitive Thiolated Chitosan Nanoparticles for Low Molecular Weight Heparin Delivery

作　　者：孙川[1] 邢洋[1] 胡华颖[1] 梁云星[1] 范博[1] 梁桂贤[1] 

机构地区：[1]山西医科大学药学院,太原030001

出　　处：《中国药学杂志》2014年第16期1414-1419,共6页Chinese Pharmaceutical Journal

基　　金：山西省自然科学基金资助项目(2014011047-4);山西省大学生创新基金(2012130)

摘　　要：目的构建低分子肝素pH敏感巯基壳聚糖纳米粒并对其进行表征;考察所构建纳米粒药物的肠黏膜透过作用。方法采用离子交联法制备低分子肝素pH敏感巯基壳聚糖纳米粒,并对其体外特性进行表征;用Franz扩散池考察纳米粒的药物黏膜累积透过量。结果纳米粒形态为类圆球形;平均粒径(329.6±7.3)nm,多相分散指数(0.185±0.01);电势(34.5±2.25)mV;包封率(97.75±0.02)%,载药量(12.463±0.003)u·mg-1;在pH 1.0介质中24 h累积释药:低分子肝素pH敏感巯基壳聚糖纳米粒<巯基壳聚糖纳米粒<药物溶液(P<0.05);在pH 6.8介质中24 h累积释药:pH敏感巯基壳聚糖纳米粒、巯基壳聚糖纳米粒均<药物溶液(P<0.05);体外8 h药物肠黏膜累积透过量:pH敏感巯基壳聚糖纳米粒、巯基壳聚糖纳米粒>pH敏感壳聚糖纳米粒>药物溶液(P<0.05),数值分别为(7.23±0.21)、(6.99±0.79)、(5.62±0.22)、(3.88±0.76)u·cm-2。结论所构建的低分子肝素pH敏感巯基壳聚糖纳米粒包封率高、粒径分布均匀,能增加低分子肝素肠黏膜透过率近1倍。OBJECTIVE To develop pH-sensitive thiolated chitosan nanoparticles and evaluate the mucosal permeation effect of the nanoparticles for low molecular weight heparin. METHODS The pH-sensitive thiolated chitosan nanoparticles were prepared by ionic cross-linking reaction and characterized for the shape, particle size, Zeta potential, drug entrapment efficiency and loading capacity. In vitro release of low molecular weight heparin from the prepared nanopartieles was evaluated in 0. 1 tool · L^-1 HC1 solution and phosphate buffered saline （PBS） at pH 6. 8 using the dialysis method. The intestinal permeability was estimated utilizing Franz diffusion cell sys- tem. RESULTS The obtained nanoparticles were found to be approximately spherical with the mean particles size of （329. 6 ± 7.3 ） nm and a positive Zeta potential of （34. 5 ± 2. 25 ） mV ; the entrapment efficiency and loading capacity of the NPs were （97. 75 ± 0. 02） % and （ 12. 463 ±0. 003） u · mg^-1 , respectively. In 0. 1 tool · L^-1 HC1 solution （pH 1.0） the release rate of low molecular weight heparin within 24 h from thiolated chitosan nanoparticles was faster than that from pH-sensitive thiolated chitosan nanoparticles with a significant difference （ P 〈 0. 05 ）. Whereas, in the case of release in PBS （ pH 6. 8 ）, no noticeable difference was observed in the drug release be- havior between pH-sensitive and non-pH-sensitive nanoparticles. The cumulative amount of permeability on carp intestine mucosa in vitro within 8 h were （7.23±0. 21）, （6. 99±0. 79）, （5. 62±0. 22） and （3. 88±0. 76） u · cm^-2 for pH-sensitive thiolated chitosan nanop- articles, thiolated chitosan nanoparticles, chitosan nanoparticles and low molecular weight heparin solution, respectively. CONCLU- SION The pH-sensitive thiolated chitosan nanoparticles have a significant penetration enhancing effect for low molecule weight heparin.

关 键 词：低分子肝素 PH敏感 巯基壳聚糖 纳米粒 黏膜透过 

分 类 号：R944[医药卫生—药剂学]