Poly(D,L-lactic-co-glycolic acid)-based artesunate nanoparticles:formulation,antimalarial and toxicity assessments  

基于聚乳酸羟乙酸共聚物的青蒿琥酯纳米颗粒的制备,及其抗疟活性和毒性评价（英文）

作　　者：Kabiru DAUDA Zulaikha BUSARI Olajumoke MORENIKEJI Funmilayo AFOLAYAN Oyetunde OYEYEMI Jairam MEENA Debasis SAHU Amulya PAND A 

机构地区：[1]Department of Zoology,University of Ibadan,Ibadan 200284,Nigeria [2]Department of Basic Sciences(Biology Programme),Babcock University,llishan-Remo 121103,Nigeria [3]Product Development Cell,National Institute of Immunology,Aruna Asaf Ali Marg,New Delhi 110067,India

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2017年第11期977-985,共9页浙江大学学报（英文版）B辑（生物医学与生物技术）

摘　　要：Objective： The aim of this study was to formulate polymer-based artesunate nanoparticles for malaria treatment. Methods： Artesunate was loaded with poly（D,L-lactic-co-glycolic acid） （PLGA） by solvent evaporation from an oil-in-water single emulsion. Nanoparticles were characterized by X-ray diffraction and differential scanning calo- rimetry analyses. In vivo antimalarial studies at 4 mg/kg were performed on Swiss male albino mice infected with Plasmodium berghei. Hematological and hepatic toxicity assays were performed. In vitro cytotoxicity of free and en- capsulated artesunate （Art-PLGA） to cell line RAW 264.7 was determined at concentrations of 7.8-1000 pg/ml. Re- sults： The particle size of the formulated drug was （329.3±21.7） nm and the entrapment efficiency was （38.4±10.1）%. Art-PLGA nanoparticles showed higher parasite suppression （62.6%） compared to free artesunate （58.2%, P〈0.05）. Platelet counts were significantly higher in controls （305 000.00±148 492.40） than in mice treated with free artesunate （139 500.00±20 506.10） or Art-PLGA （163 500.00±3535.53） （P〈0.05）. There was no sign of hepatic toxicity following use of the tested drugs. The half maximal inhibitory concentration （IC50） of Art-PLGA （468.0 pg/ml） was significantly higher （P〈0.05） than that of free artesunate （7.3 pg/ml） in the in vitro cytotoxicity assay. Conclusions： A simple treatment of PLGA-entrapped artesunate nanoparticles with dual advantages of low toxicity and better antiplasmodial efficacy has been developed.目的:为疟疾治疗制定基于聚合物的青蒿琥酯纳米粒。创新点:以聚乳酸羟乙酸共聚物(PLGA)为载体,制备青蒿琥酯纳米颗粒。并以小鼠为模型,评估其抗疟疗效和安全性。方法:以PLGA为载体,采用从单一的水包油乳剂中进行溶剂蒸发的方法制备青蒿琥酯纳米颗粒。借助X射线衍射和差示扫描量热分析对纳米颗粒进行表征。以4 mg/kg的剂量对感染疟原虫的雄性瑞士白化小鼠进行体内抗疟活性的研究,测定血液和肝毒性的相关指标。体外实验以小鼠腹腔巨噬细胞细胞系RAW 264.7为模型,在7.8~1000μg/ml浓度范围内,测定游离型和包裹型青蒿琥酯的细胞毒性。结论:实验结果表明,纳米颗粒的粒径为(329.3±21.7)nm,包封率为(38.4±10.1)%。与游离青蒿琥酯(58.2%)相比,基于PLGA的青蒿琥酯纳米颗粒(Art-PLGA)具有较高的抑虫率(62.6%),P<0.05。就血小板计数结果而言,对照组(305 000.00±148 492.40)明显地高于游离青蒿琥酯组(139 500.00±20 506.10)和Art-PLGA组(163 500.00±3535.53),P<0.05。因此,药物的使用没有导致肝毒性的产生。体外细胞毒性试验结果表明,Art-PLGA的半数抑制浓度(IC50,468.0μg/ml)显著高于游离青蒿琥酯(7.3μg/ml),P<0.05。基于PLGA的青蒿琥酯纳米颗粒是一种有效安全的抗疟治疗方法。

关 键 词：Poly（D L-lacUc-co-glycolic acid） （PLGA） Artesunate-PLGA delivery system ANTIPLASMODIAL Toxicity 

分 类 号：R943[医药卫生—药剂学] R965[医药卫生—药学]