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

关键词:  透明质酸  二硫键  黄芩苷  自载药  还原响应

Key words:  hyaluronic acid  disulfide bond  baicalin  self-loaded drug  reduction response

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，¹H-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(0.023 8±0.003 5) 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。

Abstract:

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 (¹H-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 (0.023 8±0.003 5) 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.