聚多巴胺包覆的载阿霉素羟基磷灰石纳米粒的抗肿瘤作用  

Polydopamine-coated nano-hydroxyapatite as the carrier of doxorubicin and its anti-tumor activity

作　　者：李林森 史振 白艳洁[3] 柳睿 徐晖[4] 王绍宁[2] LI Linsen;SHI Zhen;BAI Yanjie;LIU Rui;XU Hui;WANG Shaoning(School of Basic Medicine,Shenyang Medical College,Shenyang 110034,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Benxi 117004,China;Department of Stomatology,People's Hospital of Liaoning Province,Shenyang 110016,China;School of Pharmacy,Shenyang Pharmaceutical University,Benxi 117004,China)

机构地区：[1]沈阳医学院基础医学院,辽宁沈阳100034 [2]沈阳药科大学制药工程学院,辽宁本溪117004 [3]辽宁省人民医院口腔科,辽宁沈阳110016 [4]沈阳药科大学药学院,辽宁本溪117004

出　　处：《沈阳药科大学学报》2022年第11期1295-1302,共8页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省科技厅2021年辽宁省民生科技计划项目(2021JH2/10300037);沈阳医学院大学生科研课题(20189022);沈阳药科大学归国人员启动基金(GGJJ2021104)。

摘　　要：目的制备聚多巴胺包覆的载阿霉素羟基磷灰石纳米粒(PDA-DOX-nHAP),考察其对S180移植瘤的抑制作用。方法利用多巴胺在弱碱性溶液中氧化自聚合制备PDA-DOX-nHAP。通过X射线衍射仪、透射电镜、热重分析仪等对PDA-nHAP的晶相、形态、载药量等进行考察。采用直接释药法考察DOX-nHAP和PDA-DOX-nHAP体外释药特征。小鼠S180移植瘤模型瘤内注射,通过给药后肿瘤体积、重量增长率以及小鼠体重增长率等方面评价PDA-DOX-nHAP的抑瘤作用。结果PDA包覆后,药物晶体形貌、晶型未发生改变,PDA-DOX-nHAP在pH 5.0条件下12 h释放率降低29.0%(48.9%),14 d抑瘤率提高为75.01%。结论PDA的包覆使PDA-DOX-nHAP具有更好的延缓药物释放作用和抗肿瘤活性,同时减少瘤内注射药物的溢出,为降低药物毒副作用提供了选择。Objective To prepare and characterize polydopamine-coated Doxorubicin loaded nano-Hydroxyapapite(PDA-DOX-nHAP)and investigate the in vivo antitumor activity of PDA-DOX-nHAP on S180 xenograft.Methods PDA-DOX-nHAP was prepared by oxidative self-polymerization of dopamine in weakly alkaline solution.The crystal phase,morphology and drug loading of PDA-nHAP were investigated by X-ray Diffraction(XRD),Transmission Electromic Microscopy(TEM)and Thermogravimetric Analyzer(TGA).The drug release characteristics of DOX-nHAP and PDA-DOX-nHAP were investigated by direct drug release method.In vivo antitumor effect of PDA-DOX-nHAP was investigated after intratumoral injection on mice in terms of tumor volume growth rate,tumor weight growth rate and weight growth rate of mice.Results Compared with DOX-nHAP,the drug crystal morphology did not change after PDA coating.The drug release rate of PDA-DOX-nHAP decreased by 29.0%(48.9%)in 12 hours and the tumor inhibition rate increased to 75.01%in 14 days at pH 5.0.Conclusion After coating PDA,PDA-DOX-nHAP has better delaying drug release and antitumor activity.The PDA coating also could reduce the drug spillover after intratumoral injection and thus provides a choice for reducing the toxicity and side effects of chemotherapy drugs.

关 键 词：纳米羟基磷灰石 聚多巴胺 阿霉素 瘤内注射 抗肿瘤 

分 类 号：R94[医药卫生—药剂学]