【摘要】 目的:制备两亲性壳聚糖衍生物N-辛基-O,N-羧甲基壳聚糖(OCC)自组装纳米粒,并对其理化性质及安全性进行评价。方法:以透析法制备OCC自组装纳米粒;利用动态光散射(DLS)、Zeta电位仪、透射电镜对其形态、结构进行表征;通过体外溶血实验及小鼠尾静脉注射急性毒性实验评价其安全性。结果:OCC自组装纳米粒粒径为165.6 nm,多分散指数为0.191。由于纳米粒表面羧甲基基团的存在,纳米粒表面带负电荷,其表面电势为-30.2 mV。透射电镜结果显示该自组装聚合体为规则球形结构,粒径分布均匀。溶血实验和急性毒性实验结果表明,OCC溶血性远远小于Tween 80,与Cre-mophor EL相当;OCC小鼠尾静脉注射的LD50及95%可信限为560.2(523.0~600.0)mg/kg。结论:OCC自组装纳米粒可初步推断为安全可靠的静脉注射用纳米药物载体。更多还原

【Abstract】 Aim:To prepare the self-assembled nanoparticles based on carboxymethyl chitosan bearing long alkyl chains(Noctyl-O,N-carboxymethyl chitosan,OCC),characterize the physiochemical properties of OCC self-assembled nanoparticles and meanwhile evaluate the safety profile.Methods: OCC self-assembled nanoparticles were prepared by dia-lysis and characterized using dynamic light scattering,Zeta potential and transmission electron microscopy(TEM).The safety of OCC self-assembled nanoparticles was evaluated by in vitro hemolysis tests and acute toxicity in mice.Results: The mean size of self-assembled nanoparticles was 165.6 nm with polydisperse index of 0.191;The Zeta potential was-30.2 mV,which were attributed to the carboxymethyl groups on the surface of OCC self-assembled nanoparticles.The TEM images showed a spherical shape.The result of in vitro hemolysis tests showed that OCC self-assembled nanoparticles were safe carriers in terms of the induction of the membrane damage.The LD50 and its 95% confidence interval of OCC self-assembled nanoparticles in mice were 560.2(523.0～600.0) mg/kg.Conclusion: The present OCC self-assembled nanoparticles could be potentially useful as safety carriers for the intravenous drug delivery.更多还原