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

闫汉语; 张永萍; 徐剑; 刘耀; 曹国琼; 汪祖华; 宋信莉; 郭玲

doi:10.6039/j.issn.1001-0408.2022.21.07

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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

药学研究 | 更新时间：2023-02-22

- 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
- Preparation of celastrol-loaded albumin nanoparticles and their efficacy against rheumatoid arthritis
- 中国药房 2022年33卷第21期页码：2597-2602
- 作者机构：
  
  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
- 作者简介：
  
  硕士研究生。研究方向：中药及民族药新制剂、新剂型与新技术。E-mail：1689700428@qq.com
  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
- 基金信息：
  
  Δ 基金项目国家自然科学基金资助项目(81960650);贵州省高层次创新型“百”层次人才培养项目(黔科合人才〔2015〕4030号);贵州省科技计划项目(黔科合平台人才〔2017〕5655)
- DOI：10.6039/j.issn.1001-0408.2022.21.07
  中图分类号： R943;R965
- 纸质出版日期：2022-11-15，
  
  收稿日期：2022-05-22，
  
  修回日期：2022-09-22，
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闫汉语,张永萍,徐剑等.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[J].中国药房,2022,33(21):2597-2602.

YAN Hanyu,ZHANG Yongping,XU Jian,et al.Preparation of celastrol-loaded albumin nanoparticles and their efficacy against rheumatoid arthritis[J].ZHONGGUO YAOFANG,2022,33(21):2597-2602.
闫汉语,张永萍,徐剑等.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[J].中国药房,2022,33(21):2597-2602. DOI： 10.6039/j.issn.1001-0408.2022.21.07.

YAN Hanyu,ZHANG Yongping,XU Jian,et al.Preparation of celastrol-loaded albumin nanoparticles and their efficacy against rheumatoid arthritis[J].ZHONGGUO YAOFANG,2022,33(21):2597-2602. 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。

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.

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

Keywords

for- mulation technologyphysicochemical propertiesrheumatoid arthritis

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