治疗白内障的姜黄素N-三甲基壳聚糖纳米粒的制备及其初步药效学研究  

Preparation and Preliminary Efficacy of Curcumin-loaded N-Trimethyl Chitosan Nanoparticles for Cataract Treatment

作　　者：李翔 张鹏 刘亚丽[3] 杨明 张婧 

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [2]江西中医药大学创新药物与高效节能降耗制药设备国家重点实验室,江西南昌330004 [3]江西中医药大学科技学院,江西南昌330004

出　　处：《中国医药工业杂志》2017年第12期1766-1771,共6页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金(81760639;81603054;81560575;81603377);江西省自然科学基金(20151BAB215040);江西省博士后科研择优资助项目及日常资助(2016KY08;2016RC34);2016年度省杰出青年人才资助计划(20162BCB23034;20171BCB23097);中国博士后科学基金面上资助(2016M602084)

摘　　要：制备携载姜黄素(1)的N-三甲基壳聚糖(TMC)纳米粒并考察其抗大鼠硒性白内障作用。采用离子交联法制备载1的TMC纳米粒(1-NPs)。经正交设计法优化处方,再采用扫描电镜、透射电镜、粒径电位测定仪、流通池法测定1-NPs的理化性质及体外释放性能。建立大鼠硒性白内障模型,考察1-NPs对白内障形成过程中晶状体氧化程度的抑制作用。所得最佳处方为:TMC与1质量比20∶1,交联剂三聚磷酸钠(TPP)浓度为0.2%,TMC与TPP体积比为3∶1,搅拌时间为0.5 h。优化纳米粒呈球形,粒度分布均匀,ζ电位为(15.6±2.14)m V,载药量及包封率为(3.65±0.05)%和(92.5±1.3)%,体外释放具有显著缓释效应。与模型组、普通1混悬液组相比,1-NPs可显著抑制硒性白内障导致的晶状体氧化过程,升高大鼠晶状体组织中总超氧化物歧化酶和谷胱甘肽水平,降低丙二醛水平。该研究为进一步探讨1-NPs在白内障治疗中的应用提供了基础。In this study, the preparation and its preliminary efficacy on selenite-induced cataract of curcumin（1）-loaded N-trimethyl chitosan （TMC） nanoparticles （1-NPs） for ocular delivery were investigated. Firstly, 1-NPs were prepared by ionic crosslinking method through the interaction between self-synthesized TMC and sodium tripolyphosphate（TPP）. The optimized formulation was obtained by orthogonal design. The physicochemical properties of the optimal product were characterized by scanning electron microscopy （SEM）, transmission electron microscopy （TEM）, dynamic light scattering （DLS） and electrophoretic light scattering （ELS）, and flow-through cell method was employed to investigate the in vitro release behavior of 1-NPs. Secondly, the inhibition of oxidation process in selenite-induced cataract of 1-NPs in rats was investigated. The results showed that the optimal preparation for 1-NPs was as follows： weight ratio of TMC to 1 was 20∶1, TPP concentration was 0.2%, volume ratio of TMC to TPP was 3∶1, stirring time was 0.5 h. SEM and TEM observations showed that 1-NPs was spherical with good size distribution. The ζ potential, drug loading and encapsulation efficiency of the porduct were （15.6±2.14） mV, （3.65±0.05）% and （92.5±1.3）%, respectively. The release of 1 from the nanoparticles showed a sustained-release character with an obivous burst release （reaching 22.4% within 60 min）. Compared with the model group and 1 suspensions, the 1-NPs could significantly delay the lens opacification. It could significantly elevate the levels of superoxide dismutase （SOD） and reduced glutathione （GSH） in lens, and reduce the malondialdehyde （MAD） level. The lipid peroxidation in lens was strongly prevented compared with that of the group treated with 1 suspensions. Together, our findings demonstrate that the 1-loaded TMC nanoparticles with TPP as the crosslinking agent appear to be promising ophthalmic drug delivery carriers with an efficacy in delaying selenit

关 键 词：姜黄素 三甲基壳聚糖 纳米粒 正交设计 体外释放 硒性白内障 初步药效 

分 类 号：R944.9[医药卫生—药剂学]