配位交联的DOX纳米颗粒的制备与质量评价  

Preparation and Quality Evaluation of Coordination Crosslinked DOX Nanoparticles

作　　者：李西建 营双亦 李飘 史菁颖 刘宁 何玉静 Li Xijian;Ying Shuangyi;Li Piao;Shi Jingying;Liu Ning;He Yujing(School of Pharmaceutical Sciences&Institute of Materia Medica,Shandong First Medical University&Shandong Academy of Medical Sciences,Shandong,250117;National Key Laboratory of Advanced Drug Delivery and Release System,Shandong,250117)

机构地区：[1]山东第一医科大学(山东省医学科学院)药学院,山东250117 [2]先进药物递释系统全国重点实验室,山东250117

出　　处：《当代化工研究》2024年第1期149-152,共4页Modern Chemical Research

基　　金：2020年山东省大学生创新创业训练计划项目“基于pH响应性配位键的脂质体用于肿瘤多药耐药的治疗”(项目编号:S202010439120);2022年山东第一医科大学本科生研究计划(SRTP)暨大学生创新创业训练计划“配位交联的无载体纳米颗粒的制备及其抗肿瘤活性研究”(项目编号:2022104391584);2020年国家自然科学基金-青年项目“脂质过氧化物生成器用于铁凋亡介导的抗肿瘤多药耐药研究”(项目编号:82003677);2020年山东省自然科学基金-青年项目“仿转铁蛋白纳米颗粒用于铁凋亡介导的抗肿瘤多药耐药研究”(项目编号:ZR201910260053)。

摘　　要：目的:以单宁酸(TA)和三氯化铁(FeCl_(3))为载体材料,盐酸阿霉素(DOX)为主药,通过配位交联法制备纳米颗粒,并进行质量评价。方法:超声条件下将TA、FeCl_(3)、DOX依次混合制备纳米颗粒;使用粒径仪测量粒径和PDI值,并在透射电子显微镜(TEM)下观察纳米颗粒的形貌;考察纳米颗粒的稳定性及其体外药物释放行为;通过MTT法研究其在肿瘤细胞4T1上的毒性。结果:成功制备了以TA、FeCl_(3)为载体的DOX纳米颗粒(TA-Fe-DOX)。该纳米颗粒呈类球形,粒径为190nm;在一周内保持稳定;体外释放实验证明纳米颗粒在酸性环境的释药速率高于中性环境,具有明显的pH敏感性释药特征;细胞毒性实验结果表明TA-Fe空白载体没有明显毒性,而制备的TAFe-DOX纳米颗粒相对于游离药物DOX具有较高的抗肿瘤作用。结论:制备的TA-Fe-DOX纳米颗粒具有良好的pH敏感释药特性,能够提高肿瘤靶向性,为肿瘤治疗提供新的思路。Objective:Use tannic acid(TA)and ferric chloride(FeCl_(3))as the carrier material,and doxorubicin hydrochloride(DOX)as the main drug,the nanoparticles were prepared by coordination crosslinking method and evaluated for its characteristics.Methods:Under ultrasonic condition,TA,FeCl_(3) and DOX were mixed sequentially to prepare nanoparticles;measure the particle size and PDI by a particle size analyzer and observe the morphology of the nanoparticles under transmission electron microscopy(TEM);investigate the stability of nanoparticles and their in vitro drug release behavior;study its toxicity on 4T1 tumor cells using MTT assay.Results:Doxorubicin nanoparticles(TA-Fe-DOX)were successfully prepared using TA and FeCl_(3) as carriers.The particle size of the nanoparticles is 190 nm with spherical morphology and keep stable within a week;In vitro release experiments have shown that the drug release rate of nanoparticles in acidic environments is higher than that in neutral environments,indicating significant pH sensitive drug release characteristics;The results of the cytotoxicity experiment showed that the prepared TA-Fe-DOX nanoparticles had higher anti-tumor effects compared to the free DOX,while TA-Fe blank carrier had no significant toxicity.Conclusion:The prepared TA-Fe-DOX nanoparticles have good pH-sensitive drug release characteristics,which can improve tumor targeting ability and provide new ideas for tumor treatment.

关 键 词：纳米颗粒 阿霉素 单宁酸 三氯化铁 肿瘤治疗 

分 类 号：TQ[化学工程]