【作者】 陈洁； 刘青锋； 冯程程； 沈烨虹； 邵夏炎； 田志强； 周佳辰； 张奇志；

【Author】 Chenjie,Liu Qingfeng,Feng Chengcheng,Shen Yehong,Shao Xiayan,Tian Zhiqiang,Zhou Jiachen,Zhang Qizhi (Department of Pharmaceutics,School of Pharmacy,Fudan University,Shanghai 201203)

【机构】 复旦大学药学院药剂学教研室；

【摘要】 目的以香豆素-6为荧光探针,制备马铃薯凝集素修饰的PLGA纳米粒(STL-NP),并评价其经鼻入脑的靶向性。方法采用乳化/溶媒蒸发法制备纳米粒,通过表面的马来酰亚胺基与巯基化凝集素共价连接得到凝集素修饰纳米粒,并对其性质进行表征。以PLGA纳米粒(NP)为对照,比较大鼠鼻腔给予两种纳米粒后各脑组织及血液中香豆素-6的浓度。结果 STL-NP形态圆整,平均粒径(126.1±8.9)nm,zeta电位(-29.58±3.20)mV,载药量0.95%,包封率68.5%。纳米粒表面的STL仍保持与特异性糖基结合活性,其连接效率和连接密度分别为30.33%和8.026μg/mg。在pH7.4和pH4.0PBS中24h香豆素-6累积泄漏百分率<5%。STL-NP鼻腔给药后迅速吸收入血,血中AUC0→12h较NP低,而STL-NP在各脑组织的AUC0→12h为NP的1.45~1.89倍,脑靶向效率为普通纳米粒的1.89~2.45倍。结论 STL-NP能促进药物由鼻直接转运入脑,有望作为具有中枢活性的多肽蛋白药物鼻腔给药的载体。更多还原

【Abstract】 OBJECTIVE The aim of this study is to prepare Solanum tuberosum L. modified coumarin-6-loaded PLGA nanoparticles (STL-NP) and to investigate its brain targeting efficiency following intranasal administration in rats. METHODS The coumarin-6-loaded PLGA nanoparticles were prepared by emulsion/solvent evaporation technique, and then modified by conjugating the thiolated lectin to maleimides on the surface of nanoparticles. The physicochemical properties of nanoparticles were characterized.The concentrations of coumarin-6 in blood and brain tissue samples following intranasal administration of STL-NP to rats were determined and compared with those of NP. RESULTS The STL-NP were spherical with smooth surface, the mean particle size and zeta potential was (126.1±8.9) nm and (-29.58±3.20) mV. The drug loading capacity, entrapment efficiency, lectin conjugation efficiency and lectin surface concentration on nanoparticles was calculated to be 0.95%, 68.5%, 30.33% and 8.026 μg/mg, respectively. The cumulative leakage of coumarin-6 from STL-NP in vitro was less than 5% in pH7.4 and pH4.0 PBS buffer for 24h. The retaining of biorecognition activity of STL was confirmed by haemagglutination tests. The coumarin-6 in STL-NP was rapidly absorbed into blood and brain, with decreased AUC0→12h in blood(0.77-fold) as well as improved AUC0→12h in different brain tissues(1.45-1.89 times) and brain targeting efficiency ratio(1.89-2.45 times) compared with that of coumarin-6 incorporated in NP. CONCLUSION STL-NP facilitated the nose-to-brain delivery and might serve as potential carrier for therapeutic protein and peptide drugs following intranasal administration.更多还原