N-辛基-O,N-羧甲基壳聚糖自组装纳米粒的制备、理化性质及安全性评价

Preparation,physicochemical properties and safety evaluation of self-assembled nanoparticles based on N-octyl-O,N-carboxymethyl chitosan

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165．6nm，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-30．2mV。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Cremophor 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。

Aim：To prepare the self-assembled nanoparticles based on carboxymethyl chitosan bearing long alkyl chains （N-octyl-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.