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机构地区:[1]浙江中医药大学生命科学学院,杭州310053 [2]浙江中医药大学分析测试中心,杭州310053 [3]浙江中医药大学基础医学院,杭州310053
出 处:《高分子学报》2015年第6期650-656,共7页Acta Polymerica Sinica
基 金:国家自然科学基金(基金号51303163);高等学校博士学科点专项科研基金(基金号20113322120003);浙江省自然科学基金(基金号LQ12H28002,LZ14H270001,LR12H27001)资助项目
摘 要:以壳寡糖/Pluronic聚合物纳米聚集体(COPNs)、肝素为组装基元构建仿(肝素/壳聚糖)多层膜,验证多层膜负载疏水药物的可行性.PluronicP123与1,3-丙烷磺内酯反应合成末端磺酸化的Pluronic聚合物,其与PluronicF127在水溶液中自组装形成表面带负电荷的混合胶束.利用壳寡糖与混合胶束的静电作用,获得COPNs,粒径与表面电位分析、透射电镜表征COPNs为直径(27.61±2.46)nm、表面zeta电位(6.12±1.82)m V、稳定的球形结构.石英晶体微天平(QCM)跟踪检测证明COPNs与肝素可在基材表面实现交替沉积;原子力显微镜(AFM)表征多层膜表面拓扑形貌,证明COPNs在表面沉积过程中稳定.将疏水的荧光探针芘载入COPNs参与多层膜的构建,荧光光谱实验结果表明多层膜可成功包载芘,且多层膜内芘的载入量与组装层数相关.以葛根素为模型药物,载药量测定与体外释药实验结果表明多层膜具有包载和缓释疏水药物的能力.Chitosan oligosaccharide / Pluronic polymer nano-aggregates( COPNs) were designed as building blocks to fabricate( heparin / chitosan)-mimetic multilayered films,and the application of the multilayered films in loading hydrophobic drugs was investigated. Sulfonated PluronicP123 synthesized from the reaction between PluronicP123 and 1,3-propane sultone,self-assembled with PluronicF127 in aqueous solution to form mixed polymeric micelles with negatively charged sulfonic acid groups on the exterior. COPNs were obtained via the electrostatic interaction between chitosan oligosaccharide and the mixed polymeric micelles. The particle size analysis,zeta potential analysis and transmission electron microscopy( TEM) experiments demonstrated the formation of the mixed micelles and COPNs. The mean diameter and the zeta potential of COPNs were about( 27. 61 ± 2. 46) nm and( 6. 12 ± 1. 82) m V. The quartz crystal microbalance( QCM) experiment demonstrated that the layer-by-layer( LBL) films can be fabricated via alternating deposition of heparin and COPNs. The surface morphologies of the LBL films were analyzed using atomic force microscope( AFM),and the AFM images demonstrated the stability of COPNs during the LBL process. The fluorescence emission spectra verified that the hydrophobic pyrene can be incorporated by pre-encapsulation in COPNs,and the amount of pyrene in the LBL films increased with respect to the increase of the number of layers of pyreneloaded COPNs. The drug loading and release behaviors of the LBL films were investigated using puerarin as a model drug.
关 键 词:层层自组装 壳寡糖 Pluronic^(█)聚合物 混合胶束 (肝素/壳聚糖)多层膜
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