基于光热效应和pH响应性的聚多巴胺膜靶向纳米粒子的制备及性能评价  

Preparation and in vitro pharmacodynamic evaluation of polydopamine membrane-targeted nanoparticles based on photothermal effect and pH responsiveness

作　　者：张翔珂 高萌萌 陈铭 董雨萌 苏慧[1] 阎雪莹[1] ZHANG Xiangke;GAO Mengmeng;CHEN Ming;DONG Yumeng;SU Hui;YAN Xueying(School of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学药学院,黑龙江哈尔滨150040

出　　处：《药学研究》2023年第7期462-470,共9页Journal of Pharmaceutical Research

基　　金：黑龙江省自然科学基金项目(No.LH2020H096、LH2021H102)。

摘　　要：目的为构建高效、低毒、高肿瘤靶向性的乳腺癌给药系统,拟采用化疗与光疗相结合的治疗方法对乳腺癌进行治疗。方法本文以盐酸吡柔比星和多西紫杉醇作为模型药物联合使用共同负载于介孔二氧化硅(MSNs)纳米粒内,利用盐酸多巴胺(PDA)碱性条件下自身氧化在介孔二氧化硅表面形成聚多巴胺薄膜,最后通过酰胺化反应将活化后的叶酸修饰于盐酸多巴胺表面,最终制得双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒(FA-PDA-THP-DTX-MSNs)。结果通过单因素考察最终确定介孔二氧化硅载药条件:载药溶剂为25%乙醇水溶液、药物载体比为1∶1、载药时间为12 h;盐酸多巴胺包覆条件:盐酸多巴胺浓度为0.5 mg·mL^(-1)、搅拌时间为3 h。对双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒粒径、Zeta电位、傅立叶红外光谱等进行测定并与未进行修饰前介孔二氧化硅的数据进行比较,结果显示盐酸多巴胺和叶酸(FA)均成功修饰。测定最终成型的纳米粒,透射电镜下观察其形态为球形,大小均一,粒度分析仪测定结果显示,平均粒径为(201.4±21.7)nm,PDI指数为0.264,Zeta电位为(+23.3±0.67)mV,盐酸吡柔比星(THP)和多西紫杉醇D(DTX)的载药量分别为(11.77%±0.33%)、(5.72%±0.25%),THP和DTX的包封率分别为(36.92%±0.44%)、(36.02%±0.68%)。双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒给药系统体外释放实验结果显示双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒中药物具有良好的缓释性能和酸响应性并且在近红外激光的照射条件下能够实现药物的突释。结论本研究可为聚多巴胺膜包覆双载药光热型纳米粒的抗肿瘤研究提供更加丰富的实验依据,为开发新型纳米粒奠定基础。Objective In order to construct a drug delivery system with high efficiency,low toxicity,and high tumor targeting,the combination of chemotherapy and phototherapy was proposed to treat breast cancer in this experiment.Methods In this paper,pirarubicin hydrochloride(THP)and docetaxel(DTX)were used as model drugs,which were co-loaded in mesoporous silica nanoparticles(MSNs),and self-oxidation of dopamine hydrochloride under alkaline conditions was used to form polystyrene on the surface of MSNs.Finally,the activated folic acid(FA)was modified on the surface of PDA by amidation reaction,and finally double-loaded folic acid-modified polydopamine membrane-coated mesoporous silica nanoparticles(FA-PDA-THP-DTX-MSNs)were prepared.Results The drug loading conditions of MSNs were determined by single factor method:the drug loading solvent was 25%ethanol solution,the ratio of drug carrier was 1∶1,and the drug loading time was 12 h.The coating conditions of polydopamine membrane were as follows:the concentration of dopamine hydrochloride was 0.5 mg·mL^(-1)and the stirring time was 3 h.The particle size,Zeta potential and Fourier transform infrared spectroscopy of FA-PDA-THP-DTX-MSNs were determined and compared with those of unmodified MSNs.The results showed that PDA and folic acid were modified successfully.The characterization of the final formed nanoparticles was determined,and its shape was spherical and uniform under transmission electron microscope.The results of particle size analyzer showed that the average particle size was(201.4±21.7)nm,and the Zeta potential was about(+23.3±0.67)mV.The drug loading of THP and DTX were 11.25%and 5.57%,respectively.The encapsulation efficiencies of THP and DTX were(36.92%±0.44%)and(36.02%±0.68%),respectively.The results of drug release in vitro show that the drug in FA-PDA-THP-DTX-MSNs has good sustained release performance and acid response performance,and can achieve sudden drug release under the condition of near-infrared laser irradiation.Conclusion It can provide more a

关 键 词：聚多巴胺 盐酸吡柔比星 多西紫杉醇 PH响应 叶酸 

分 类 号：R943[医药卫生—药剂学]