DiR-PEG-PLGA荧光纳米囊的制备、表征及体外生物相容性评价  

Preparation,Characterization and Biocompatibility Evaluation in vitro of DiR-PEG-PLGA Fluorescent Nanocapsules

作　　者：程欣[1,2] 柯瑾[1] 陈烁[3] 谢薇[4] 邵长丽[5] 侯安国[1] 张昆[1] 邓林[1] 陈艳五 马云淑[1,2] CHENG Xin;KE Jin;CHEN Shuo;XIE Wei;SHAO Changli;HOU Anguo;ZHANG Kun;DENG Lin;CHEN Yanwu;MA Yunshu(College of TCM,Yunnan University of TCM,Kunming 650500,China;Yunnan University of TCM/Yunnan Key Lab of Dai and Yi Medicines,Kunming 650500,China;Ultrasound Department,Yunnan Hospital of TCM,Kunming 650011,China;College of Basic Medicine,Yunnan University of TCM,Kunming 650500,China;College of Acupuncture Massage and Rehabilitation,Yunnan University of TCM,Kunming 650500,China)

机构地区：[1]云南中医学院中药学院,昆明650500 [2]云南中医学院/云南省傣医药与彝医药重点实验室,昆明650500 [3]云南省中医医院超声科,昆明650011 [4]云南中医学院基础医学院,昆明650500 [5]云南中医学院针灸推拿康复学院,昆明650500

出　　处：《中国药房》2018年第8期1031-1035,共5页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81673682);云南省科技计划项目[No.2015FB205(-003);2017FF117(-017)];云南省重点实验室培育计划项目(No.2017DG006);云南省教育厅大学生创新创业训练计划项目(No.2016013)

摘　　要：目的:制备并表征包载荧光染料1,1′-二十八烷基-3,3,3′,3′-四甲基吲哚三碳花青碘(Di R)的聚乙二醇-聚乳酸-羟基乙酸共聚物(Di R-PEG-PLGA)纳米囊,评价其体外生物相容性。方法:以聚乳酸-羟基乙酸共聚物(PLGA)、聚乙二醇(PEG)-PLGA共混物为载体,采用改良的超声乳化法制备Di R-PEG-PLGA纳米囊样品。对样品的粒径、Zeta电位、形貌、稳定性、体外荧光特性等进行检测;采用MTT试验评价样品对人源性HL7702肝细胞的体外细胞毒性,采用体外溶血试验考察其对健康Wistar大鼠血细胞的溶血作用。结果:所制备的Di R-PEG-PLGA纳米囊呈圆球形,具有明显核壳结构,平均粒径为(507.53±7.87)nm,粒径的多分散系数为0.306 1±0.001 5,Zeta电位为(-35.20±0.92)m V;4℃条件下保存6个月,稳定性较好;体外荧光信号强度(y)随Di R质量浓度(x)呈线性增加,线性方程为y=0.345 2x+0.433 4(R2=0.997 3)。所制纳米囊对HL7702细胞的毒性为0~1级(即无细胞毒性),对大鼠血细胞无体外溶血作用。结论:本研究成功制备了具有荧光特性的Di R-PEG-PLGA纳米囊;所制纳米囊体外生物相容性较好,有望成为一种安全的药物光学示踪载体。OBJECTIVE:To prepare and characterize Fluorescent dye 1,1′-octacosyl-3,3,3′,3′-tetramethylindocarbocyanine iodide(DiR)-loading polyethylene glycol-poly lactic-co-glycolic acid(DiR-PEG-PLGA)nanocapsules,and to evaluate its biocompatibility in vitro.METHODS:Using PLGA and PEG-PLGA as carrier,DiR-PEG-PLGA nanocapsules were prepared by modified ultrasonic emulsification method.The particle size,Zeta potential,morphology,stability and fluorescence in vitro of nanocapsules were detected respectively.MTT assay was used to evaluate cytotoxicity in vitro of nanocapsules to human-derived HL7702 hepatocytes,and hemolysis test was carried out to investigate its hemolysis effects.RESULTS:Prepared DiR-PEG-PLGA nanocapsules were spherical with a clear core-shell structure.The average particle size was(507.53±7.87)nm,polydispersity coetficient of particle size was 0.306 1±0.001 5 and Zeta potential was(-35.20±0.92)mV with good stability within 6 months under 4℃.Fluorescence signal intensity(y)of nanocapsules was increased linearly with DiR mass concentration(x)in vitro.The linear eguation was y=0.345 2x+0.433 4(R2=0.997 3).The toxicity of nanocapsules to HL7702 cells was between 0-1 degree,and no hemolytic effect was observed.CONCLUSIONS:The study successfully prepare fluorescent DiR-PEG-PLGA nanocapsules with high biocompatibility in vitro,which is further expected to become a safe optical drug carrier.

关 键 词：纳米囊 超声乳化法 荧光 表征 生物相容性 DIR 聚乙二醇 聚乳酸-羟基乙酸共聚物 

分 类 号：R94[医药卫生—药剂学] R283.6[医药卫生—药学]