首页|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

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

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过氧化氢(hydrogen peroxide,H2O2)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H2O2/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H2O2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。
Preparation and in vitro evaluation of polylactic acid nanoparticles containing arginine and glucose oxidase
Hydrogen peroxide(H2O2)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 H2O2/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 H2O2 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.

L-arginineglucose oxidasepolylactic acidhydrogen peroxidenitric oxide

杨美洋、陈伟军、邱立朋、陈敬华

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江南大学生命科学与健康工程学院,江苏无锡 214122

江南大学化学与材料工程学院,江苏无锡 214122

L-精氨酸 葡萄糖氧化酶 聚乳酸 过氧化氢 一氧化氮

国家重点研发计划

2021YFC2103100

2024

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子:1.274
ISSN:0513-4870
年,卷(期):2024.59(1)
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