【摘要】 目的制备载穿心莲二萜内酯有效部位的透明质酸-苯硼酸纳米粒。方法酰胺反应合成透明质酸-苯硼酸后,溶剂挥发法制备纳米粒,并进行表征。MTT法检测体外细胞毒性,HPLC法测定细胞摄取效率,UPLC-MS/MS法考察药动学行为。结果所得纳米粒呈球形,形态均一,平均粒径为(112.3±0.92)nm,Zeta电位为-48.4 mV,载药量为(47.50±0.62)%,包封率为(90.1±1.60)%,30 d内稳定性良好,24 h内累积释放度为90%。与原料药相比,纳米粒对HepG2、A549、MCF-7细胞的细胞毒性显著增强(P<0.05,P<0.01),摄取量显著升高(P<0.05),并呈时间依赖性。纳米粒体内消除缓慢,延长了药物循环时间。结论载穿心莲二萜内酯有效部位的透明质酸-苯硼酸纳米粒具有较强的体外抗肿瘤活性,并可促进大鼠体内药物吸收和生物利用度。更多还原

【Abstract】 AIM To prepare the hyaluronic acid-phenylboronic acid nanoparticles loaded with effective parts of Andrographis paniculata(Burm. f.) Nees. diterpene lactones.METHODS Hyaluronic acid-phenylboronic acid synthesized by amide reaction was prepared into nanoparticles by solvent evaporation method, after which characterization was achieved. In vitro cytotoxicity was detected by MTT assay, celluar uptake efficiency was determined by HPLC, and pharmacokinetic behaviors were investigated by UPLC-MS/MS.RESULTS The obtained spherical nanoparticles displayed uniform morphology, demonstrating the average particle size of(112.3±0.92) nm, Zeta potential of-48.4 mV, drug loading of(47.50±0.62)%, encapsulation efficiency of(90.1±1.60)%, good stability within 30 d, and accmulative release rate of 90% within 24 h. Compared with raw medicine, the nanoparticles displayed significantly enhanced cytotoxicities on HepG2, A549 and MCF-7 cells(P<0.05, P<0.01), along with markedly increased uptake efficiency(P<0.05) in a time-dependent manner. The slow in vivo elimination of nanoparticles could prolong drug circulation time. CONCLUSION Exhibiting strong in vitro anti-tumor activity, the hyaluronic acid-phenylboronic acid nanoparticles loaded with effective parts of A. paniculata diterpene lactones can promote the in vivo absorption and bioavailability of drug in rats.更多还原