载精氨酸和葡萄糖氧化酶的聚乳酸纳米粒子制备与体外评价  

Preparation and in vitro evaluation of polylactic acid nanoparticles containing arginine and glucose oxidase

作　　者：杨美洋 陈伟军 邱立朋 陈敬华 YANG Mei-yang;CHEN Wei-jun;QIU Li-peng;CHEN Jing-hua(School of Life Science and Health Engineering,Jiangnan University,Wuxi 214122,China;School of Chemical and Material Engineering,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学生命科学与健康工程学院,江苏无锡214122 [2]江南大学化学与材料工程学院,江苏无锡214122

出　　处：《药学学报》2024年第1期225-231,共7页Acta Pharmaceutica Sinica

基　　金：国家重点研发计划项目(2021YFC2103100)。

摘　　要：过氧化氢(hydrogen peroxide,H_(2)O_(2))和一氧化氮(nitric oxide,NO)由于其在生理环境中的半衰期短、生物利用度低、肿瘤靶向性差和全身不良反应限制了它们的应用。本研究采用超声乳化-纳米沉淀法合成了载有L-精氨酸(L-arginine,L-Arg)和葡萄糖氧化酶(glucose oxidase,GOx)的双十烷基二甲基溴化铵(didecyl dimethyl ammonium bromide,DDAB)/聚乳酸(polylactic acid,PLA)纳米粒子(GADP),并考察了体外抗肿瘤活性。通过静电吸附作用使其表面吸附GOx,对纳米粒子的粒径、电位、包埋率、产生H_(2)O_(2)/NO的能力等性能进行考察,同时采用人肝癌细胞(HepG2)进行体外抗肿瘤效果评价。结果显示,制备的L-Arg-DDAB/PLA(ADP)纳米粒子为粒径225.7±6.33 nm的球形粒子,电位为+23.5±0.12 mV,GOx的吸附率为87.23%±0.02%,L-Arg的载药量为15.6%±0.22%。通过测定葡萄糖溶液pH值的变化和H_(2)O_(2)的量表明,GADP具有良好的催化活性。体外细胞实验表明,空白纳米粒子DDAB/PLA对细胞毒性较小,载药纳米粒子GADP对肿瘤细胞具有较强的杀伤作用,并能抑制肿瘤细胞迁移。低剂量的纳米级NO递送系统GADP能够有效地抑制肿瘤细胞的迁移,杀伤肿瘤细胞,从而产生治疗益处。Hydrogen peroxide(H_(2)O_(2))and nitric oxide(NO)has a short half-life,low bioavailability,poor tumor targeting and systemic adverse reactions in the physiological environment.In this study,phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide(DDAB)/polylactic acid nanoparticles(PLA),then L-arginine(L-Arg)and glucose oxidase(GOx)-loaded nanoparticles(GADP)were prepared,and the in vitro antitumor activity was investigated.The particle size,potential,embedding rate and the ability to produce H_(2)O_(2)/NO of the nanoparticles were investigated.Meanwhile,in vitro cell cytotoxicity against human hepatoma cells(HepG2)was evaluated.The results showed that the prepared L-Arg-DDAB/PLA(ADP)nanoparticles were spherical particles.And the particle size and zeta potential were(225.7±6.33)nm and(+23.5±0.12)mV,respectively.The adsorption rate of GOx was 87.23%±0.02%.The drug loading of L-Arg was 15.6%±0.22%.The pH value of glucose solution and the amount of H_(2)O_(2)showed that GADP had good catalytic activity.In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic,while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells.And can inhibit tumor cell migration.The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells,thus producing therapeutic benefits.

关 键 词：L-精氨酸 葡萄糖氧化酶 聚乳酸 过氧化氢 一氧化氮 

分 类 号：R944[医药卫生—药剂学]