紫杉醇PLGA纳米粒的表征及体外抗肿瘤作用研究  

Characterization of paclitaxel-PLGA nanoparticles and their antitumor effects in vitro

作　　者：王晓静 郭子硕 张海桐 陈宛灵 李加玲 杜守颖[1] 李鹏跃[1] WANG Xiaojing;GUO Zishuo;ZHANG Haitong;CHEN Wanling;LI Jialing;DU Shouying;LI Pengyue(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《中国药房》2024年第22期2721-2725,共5页China Pharmacy

基　　金：国家自然科学基金项目(No.82274111,No.81803738)。

摘　　要：目的表征紫杉醇纳米粒(PTX-PLGA-NPs),并评价其对Lewis肺癌细胞的体外抑制作用。方法对以乳化溶剂挥发法所制PTX-PLGA-NPs的粒径、多分散性指数(PDI)、Zeta电位、微观形态、包封率、载药量、紫外-可见光吸收特性、稳定性等进行表征;以小鼠Lewis肺癌细胞为对象,以PTX对照品为参照,分别采用CCK-8法、Calcein-AM/PI双染法检测PTX-PLGA-NPs的细胞毒性和体外杀伤活性,分别采用AnnexinⅤ-FITC/PI染色法、PI染色法评估PTX-PLGA-NPs对细胞凋亡及周期的影响。结果PTXPLGA-NPs呈类球形,平均粒径为(172.03±0.95)nm,PDI为0.098±0.012,Zeta电位为(-1.76±0.02)mV;包封率和载药量分别为(52.32±0.66)%、(7.07±0.18)%,紫外-可见光吸收特征不受载体聚乳酸-羟基乙酸共聚物的影响;4℃下避光放置7 d时,其粒径无明显变化,平均PDI(放置1、2、4、7 d)均小于0.3。与PTX对照品组相比,PTX-PLGA-NPs组有更多细胞处于死亡状态,其存活率(当PTX质量浓度为11.2μg/mL时)显著降低,凋亡率和G2期细胞比例均显著升高(P<0.05)。结论所制PTX-PLGA-NPs粒径均一、分散均匀、性质稳定,对肺癌细胞的体外杀伤作用较PTX强。OBJECTIVE To characterize paclitaxel nanoparticles(PTX-PLGA-NPs)and evaluate their in vitro inhibitory effect on Lewis lung cancer cells.METHODS The PTX-PLGA-NPs prepared by the emulsion-solvent evaporation method were characterized in terms of particle size,polydispersity index(PDI),Zeta potential,microscopic morphology,encapsulation efficiency,drug loading,ultraviolet-visible absorption characteristics and stability.Using mouse Lewis lung cancer cells as the subjects and paclitaxel reference substance as the control,the cytotoxicity and in vitro killing activity of PTX-PLGA-NPs were detected using CCK-8 method and Calcein-AM/PI double staining method,respectively.The effects of PTX-PLGA-NPs on cell apoptosis and cell cycle were assessed by AnnexinⅤ-FITC/PI staining method and PI staining method,respectively.RESULTS PTX-PLGA-NPs were spherical with an average particle size of(172.03±0.95)nm,PDI of 0.098±0.012,and Zeta potential of(-1.76±0.02)mV.The encapsulation efficiency and drug loading were(52.32±0.66)%and(7.07±0.18)%,respectively,and the ultraviolet-visible absorption characteristics were not affected by the carrier polylactic-co-glycolic acid.When stored in the dark at 4℃for 7 days,no significant change was noted in particle size,and the average PDI(after 1,2,4 and 7 days of storage)was under 0.3.Compared with the paclitaxel reference substance group,the PTX-PLGA-NPs group had more cells in a state of death,the survival rate(at the PTX concentration of 11.2μg/mL)was significantly decreased,and both the apoptosis rate and the proportion of G2 phase cells were significantly increased(P<0.05).CONCLUSIONS The prepared PTX-PLGA-NPs indicate homogeneity in particle size,uniform dispersion,stable properties,and stronger in vitro killing effect on lung cancer cells than PTX.

关 键 词：紫杉醇 聚乳酸-羟基乙酸共聚物 纳米粒 表征 LEWIS肺癌细胞 体外抗肿瘤作用 

分 类 号：R944[医药卫生—药剂学] R979.1[医药卫生—药学]