Page 43 - 《中国药房》2022年21期

雷公藤红素白蛋白纳米粒的制备及抗类风湿性关节炎药效评价 Δ

闫汉语 ，张永萍，徐 剑，刘 耀，曹国琼，汪祖华，宋信莉，郭 玲（贵州中医药大学药学院/国家苗药工程技术
＊
#
研究中心/贵州省中药民族药炮制与制剂工程技术研究中心，贵阳 550025）

中图分类号 R943；R965 文献标志码 A 文章编号 1001-0408（2022）21-2597-07
DOI 10.6039/j.issn.1001-0408.2022.21.07

摘 要 目的 制备雷公藤红素白蛋白纳米粒（CLT-AN），并考察其体内抗类风湿性关节炎（RA）活性。方法 采用超声法制备
CLT-AN，以粒径、分散指数（PDI）和稳定性为评价指标，以CLT投药量、大豆油用量和超声功率为考察因素，通过单因素实验优化
处方工艺。利用透射电镜、激光粒度测定仪等考察CLT-AN的理化性质，并研究其体外稳定性和体外释放特性。构建佐剂诱导关
节炎大鼠模型，考察CLT-AN对模型大鼠关节肿胀、血清中炎症因子[肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）]水平以及
关节组织病理状态的影响。结果 优化的处方为CLT 6.5 g、大豆油45 mg、超声功率490 W、超声时间8 min。按最佳处方制备的
CLT-AN 外观形态圆整，平均粒径为（96.8±1.1）nm，PDI 为 0.174±0.020，Zeta 电位为（－18.6±1.7）mV，包封率为（94.61±
0.46）%，载药量为（2.42±0.21）%。在室温条件下，CLT-AN储存5 d内的粒径、PDI、Zeta电位和包封率均无显著变化。CLT-AN体
外释放缓慢，72 h的累积释放量可达到73.56%；与游离CLT相比，CLT-AN可明显抑制模型大鼠的关节肿胀，降低其血清中TNF-
α、IL-1β水平，并且显著改善炎症关节组织的病理状态。结论 超声法制备的CLT-AN粒径适中、稳定性良好，具有显著的缓释特
征和优良的抗RA活性。
关键词 雷公藤红素白蛋白纳米粒；处方工艺；理化性质；类风湿性关节炎

Preparation of celastrol-loaded albumin nanoparticles and their efficacy against rheumatoid arthritis
YAN Hanyu，ZHANG Yongping，XU Jian，LIU Yao，CAO Guoqiong，WANG Zuhua，SONG Xinli，GUO Ling
（School of Pharmacy/National Engineering Technology Research Center of Miao Medicine/Guizhou Engineering
Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic
Medicine，Guizhou University of Traditional Chinese Medicine，Guiyang 550025，China）

ABSTRACT OBJECTIVE To prepare celastrol-loaded albumin nanoparticles（CLT-AN），and to investigate their activity against
rheumatoid arthritis （RA） in vivo. METHODS CLT-AN was prepared by ultrasonic method. The formulation technology was
optimized by single-factor test by taking particle size，polydispersity index（PDI）and stability as indexes，with the dosage of CLT，
the dosage of soybean oil and the ultrasonic power as factors. The physical and chemical properties of CLT-AN were investigated by
transmission electron microscopy（TEM）and laser particle size analyzer；in vitro stability and release profile were studied. A rat
model of adjuvant-induced arthritis was constructed to investigate the effects of CLT-AN on joint swelling，the levels of serum
inflammatory factors [tumor necrosis factor α（TNF-α）and interleukin-1β（IL-1β）] and pathological state of joint tissue.
RESULTS The optimized formulation was CLT 6.5 g，soybean oil 45 mg，ultrasonic power 490 W，ultrasonic time 8 min. CLT-
AN prepared by the best formulation showed uniform and spherical morphology. Its particle size，PDI，Zeta potential were（96.8±
1.1） nm，0.174±0.020，and （－18.6±1.7） mV，respectively. The encapsulation efficiency and drug-loading efficiency were
（94.61±0.46）% and（2.42±0.21）% . There were no significant changes in particle size，PDI，Zeta potential and encapsulation
efficiency of CLT-AN within 5 days of storage at room temperature. CLT-AN was slowly released in vitro，and the cumulative
release reached 73.56% in 72 h. Compared with CLT，CLT-AN could significantly inhibit the joint swelling of model rats，reduced
the levels of inflammatory factors TNF-α and IL-1β in serum，and improved the pathological state of inflammatory joint tissue.
CONCLUSIONS CLT-AN prepared by ultrasonic method has the appropriate particle size，good stability，significant sustained-
release characteristics，and excellent therapeutic efficacy against RA.
KEYWORDS celastrol-loaded albumin nanoparticles；for- mulation technology；physicochemical properties；rheumatoid arthritis

Δ 基金项目 国家自然科学基金资助项目（No.81960650）；贵州省
高层次创新型“百”层次人才培养项目（No. 黔科合人才〔2015〕4030 类风湿性关节炎（rheumatoid arthritis，RA）是一种伴
号）；贵州省科技计划项目（No.黔科合平台人才〔2017〕5655） 有炎症细胞浸润与进行性关节损伤的慢性自身免疫性
＊第一作者 硕士研究生。研究方向：中药及民族药新制剂、新剂 疾病 。由于炎症的反复发作以及关节软骨、肌腱的持
[1]
型与新技术。E-mail：1689700428@qq.com
续破坏，最终会造成关节功能障碍，甚至残废，严重影响
# 通信作者 副教授，硕士生导师，博士。研究方向：中药及民族药
新制剂、新剂型与新技术。E-mail：glgwz1989@163.com 患者的生活质量和寿命。雷公藤红素（celastrol，CLT）是

中国药房 2022年第33卷第21期 China Pharmacy 2022 Vol. 33 No. 21 ·2597·