聚多巴胺-砒霜纳米递药系统的构建及其抑瘤效果  

Construction and evaluation of anti-tumor effect of polydopamine-arsenic nanodrug delivery system

作　　者：袁一超 王春梅 李策 张纪平 费芸萱 高韩怡 马意琳 郑杭生[1] 朱志红 YUAN Yi-chao;WANG Chun-mei;LI Ce;ZHANG Ji-ping;FEI Yun-xuan;GAO Han-yi;MA Yi-lin;ZHENG Hang-sheng;ZHU Zhi-hong(School of Pharmacy,Zhejiang Chinese Medical University,Hangzhou 311400,China;Kecheng District Hospital of Traditional Chinese Medicine,Quzhou 324000,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州311400 [2]衢州市柯城区中医医院,浙江衢州324000

出　　处：《中草药》2023年第23期7759-7764,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金青年科学基金项目(82003954);浙江省自然科学基金资助项目(LY23H280010);浙江省大学生科技创新活动计划(新苗人才计划)(2023R410040);2023年浙江中医药大学校级科研项目(2023JKZKTS23)。

摘　　要：目的 通过制备聚多巴胺的砒霜纳米递药系统(polydopamine-arsenic trioxide nano-drug delivery system,PDA-ATO@NDDS)来提高砒霜治疗肿瘤的疗效。方法 在碱性条件下制备搭载砒霜的聚多巴胺纳米粒(PDA-ATO@NDDS),利用单因素考察法优化合成条件;通过透射电子显微镜(transmission electron microscope,TEM)、激光粒度仪表征纳米粒大小;采用透析袋法考察其体外释药特性;采用电感耦合等离子发射光谱(inductive coupled plasma emission spectrometer,ICP)测定其包封率与载药量;并对其体内外抗肿瘤效果进行考察。结果 PDA-ATO@NDDS的最佳合成条件为PVP用量0.5 g,MnCl2与ATO用量比为1∶5,孵育时间4 h;制备的PDA-ATO@NDDS在TEM下外观呈圆形或类圆形,平均粒径为(243.5±3.5)nm,多分散指数(polydispersity index,PDI)为0.229±0.011;包封率和载药量分别为(8.74±0.03)%和(14.21±0.06)%;体外释放度考察显示,砒霜纳米粒具有一定的缓释效果。细胞毒性实验表明,在低浓度下PDA-ATO@NDDS对细胞具有较强毒性(P<0.01)。体内药效学表明,ATO与PDA-ATO@NDDS对小鼠肿瘤的抑制具有显著性差异(P<0.05),PDA-ATO@NDDS具有较好的肿瘤抑制作用。结论 PDA-ATO@NDDS递药系统提高了砒霜治疗肿瘤的疗效,为砒霜新型递药系统的构建及其在肿瘤治疗中的应用提供参考。Objective To improve the efficacy of arsenic in the treatment of tumors by preparing a polydopamine-arsenic trioxide nano-drug delivery system(PDA-ATO@NDDS).Methods PDA-ATO@NDDS were prepared under alkaline conditions,and the synthesis conditions were optimized by single-factor method;The size of PDA-ATO@NDDS was characterized by transmission electron microscope(TEM)and laser particle size measurement;The in vitro drug release characteristics were investigated by dialysis bag method;the encapsulation rate and drug loading were determined by inductively coupled plasma emission spectrometer(ICP);And the in vitro and in vivo anti-tumor effects were investigated.Results The optimal synthesis conditions of PDA-ATO@NDDS were 0.5 g of PVP,1:5 of MnCl2:ATO,and 4 h of incubation time;the prepared PDA-ATO@NDDS had a round or round-like appearance with an average particle size of(243.5±3.5)nm and PDI of 0.229±0.011.The encapsulation rate and drug loading was(8.74±0.03)%and(14.21±0.06)%,respectively;The in vitro release study showed that PDA-ATO@NDDS could delay the release of arsenic.Cytotoxicity experiments showed that PDA-ATO@NDDS had the strongest toxic to cells at low concentrations(P<0.01).In vivo pharmacodynamics showed PDA-ATO@NDDS had a better tumor inhibitory effect compared to ATO(P<0.05).Conclusion The PDA-ATO@NDDS improved the anti-tumor efficacy of arsenic,and provided a reference for the construction of a novel drug delivery system for arsenic and its application in tumor therapy.

关 键 词：砒霜 聚多巴胺 药效学评价 抗肿瘤 纳米递药系统 

分 类 号：R283.6[医药卫生—中药学]