还原响应型靶向自载药纳米粒的制备及其体外评价  

Preparation and in Vitro Evaluation of Reduction-responsive Targeting Self-loaded Nanoparticle

作　　者：郭切切 张舒迪 邵艳寻 郭晨曦 杨雅欣 刘占军 GUO Qieqie;ZHANG Shudi;SHAO Yanxun;GUO Chenxi;YANG Yaxin;LIU Zhanjun(College of Pharmacy,North China University of Science and Technology,Tangshan 063210,China)

机构地区：[1]华北理工大学药学院,河北唐山063210

出　　处：《中国现代应用药学》2022年第19期2511-2520,共10页Chinese Journal of Modern Applied Pharmacy

基　　金：河北省自然科学基金(H2021209024,H2018209347)。

摘　　要：目的制备靶向性的自载药纳米粒(HA-ss-Bai NPs),并考察其作为药物载体递送姜黄素(curcumin,Cur)的可行性。方法制备二硫键连接的透明质酸(hyaluronic acid,HA)-黄芩苷(baicalin,Bai)聚合物,利用核磁共振氢谱(hydrogen nuclear magnetic resonance spectroscopy,^(1)H-NMR)、红外光谱(infrared spectroscopy,IR)确证聚合物的结构;采用超声法制备自组装纳米粒,并对其粒径、Zeta电位进行表征;采用芘荧光探针法测定纳米粒的临界聚集浓度(critical aggregation concentration,CAC);测定载Cur纳米粒包封率和载药量;MTT试验考察载药纳米粒的体外抗肿瘤活性。结果制备HA-ss-Bai NPs,最小粒径为(124.3±6.5)nm,CAC值为(0.0238±0.0035)mg·mL^(–1)。测得Cur/HA-ss-Bai NPs的粒径为(172.5±3.2)nm,载药量为(17.08±0.25)%,包封率为(51.23±3.97)%。体外释放表明药物在还原条件下可快速释放,MTT试验表明Cur/HA-ss-Bai NPs对HepG2肝癌细胞生长具有显著的抑制作用。结论制备的Cur/HA-ss-Bai NPs粒径均匀、载药量较高,具有良好的还原响应性和抗肿瘤活性,同时提高了Bai与Cur的体外抗肿瘤效果。OBJECTIVE To prepare self-loaded drug nanoparticles(HA-ss-Bai NPs)with reduction responsiveness and tumor-targeting properties,and to investigate their feasibility as a drug carrier to deliver curcumin(Cur).METHODS The polymer hyaluronic acid(HA)-baicalin(Bai)connected by disulfide bonds was synthesized,and its structure was confirmed by hydrogen nuclear magnetic resonance spectroscopy(^(1)H-NMR)and infrared spectroscopy(IR).The self-assembled nanoparticles were prepared by the ultrasound method,their particle size and Zeta potential were characterized,and their critical aggregation concentration(CAC)was determined by the pyrene fluorescence probe method;the encapsulation efficiency and drug loading amount of nanoparticles loaded with Cur were determined.The anti-tumor activity in vitro of drug-loaded nanoparticles was assessed by MTT assay.RESULTS HA-ss-Bai NPs were prepared,the minimum particle size was(124.3±6.5)nm,CAC value was(0.0238±0.0035)mg·mL^(–1).The particle size of Cur/HA-ss-Bai NPs was(172.5±3.2)nm,drug loading was(17.08±0.25)%,encapsulation efficiency was(51.23±3.97)%.The in vitro release showed that the drug could be released quickly under reducing conditions.The MTT experiment indicated that Cur/HA-ss-Bai NPs had a significant inhibitory effect on the growth of HepG2 liver cancer cells.CONCLUSION The Cur/HA-ss-Bai NPs have uniform particle size,with high drug loading,good reduction responsiveness and anti-cancer activity.The anti-tumor effect of Bai and Cur in vitro is improved.

关 键 词：透明质酸 二硫键 黄芩苷 自载药 还原响应 

分 类 号：R943[医药卫生—药剂学]