摘要
目的 通过制备青藤碱纳米晶自稳定Pickering乳液(sinomenine nanocrystals self-stabilized Pickering emulsions,SinNSSPE)关节腔注射剂,在关节腔内形成药物贮库,缓慢释放以提高生物利用度,降低药物毒副作用,以青藤碱纳米晶(sinomeninenanocrystal,Sin-NCs)自身为稳定剂制备Sin-NSSPE关节腔注射剂,用药效学实验考察其对类风湿性关节炎(rheumatoid arthritis,RA)的治疗效果。方法 通过药物质量浓度、油水相比例和水相pH值等因素对Sin-NSSPE进行优化,运用福氏佐剂关节炎方法建立RA大鼠模型,以关节肿胀度、关节炎指数、脾指数、酶联接免疫吸附剂测定(enzyme-linked immunosorbnent assay,ELISA)、组织病理学检查、Western blotting法作为指标进行检测。结果 结果显示Sin-NSSPE的粒径均匀,载药量良好,Sin-NCs的平均粒径为(121.49±18.26)nm、Sin-NSSPE的粒径为(1 159.60±160.15)nm、载药量4.92mg/mL;药效学实验结果显示,与青藤碱ig组相比,Sin-NSSPE关节腔注射组能有效降低关节肿胀度和炎症指数,改善滑膜组织的病变、抑制关节炎症。青藤碱关节腔注射组和Sin-NSSPE关节腔注射组均能明显改善大鼠关节肿胀,降低滑膜组织中炎症因子白细胞介素-1(interleukin-1,IL-1)、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达(P<0.05、0.01),且Sin-NSSPE关节腔注射组治疗效果优于青藤碱关节注射组,同时剂型稳定性提高并形成药物贮库,使药效更加平稳。结论 制备的Sin-NSSPE性质稳定,Sin-NSSPE关节腔注射对大鼠RA有良好的疗效。
Objective Sinomenine nanocrystals self-stabilized Pickering emulsions(Sin-NSSPE) injection was prepared for joint cavity,and a drug depot was formed in the joint cavity,which was slowly released to improve the bioavailability and reduce the toxic and side effects of the drug. Sin-NSSPE injection was prepared with sinomenine nanocrystalline(Sin-NCs) itself as a stabilizer,and the therapeutic effect on rheumatoid arthritis(RA) was investigated by pharmacodynamic experiments. Methods Sin-NSSPE was optimized by factors such as drug concentration,oil-water ratio and pH of water phase,and RA model was established in SD rats with Freund’s adjuvant arthritis method. Toe swelling,arthritis index,spleen index,histopathological examination and Western blotting method were used as indicators for detection. Results The results showed that Pickering emulsion had uniform particle size and good drug loading,the average particle size of Sin-NCs was(121.49 ± 18.26) nm,the particle size of Sin-NSSPE was(1 159.60 ±160.15) nm,and the drug loading was 4.92 mg/mL. Pharmacodynamics experiments showed that,compared with the intragastric administration of sinomenine,Sin-NSSSPE joint cavity injection group can effectively reduce joint swelling and inflammation index,improve synovial tissue lesions and inhibit joint inflammation. Both the sinomenine intra-articular injection group and the SinNSSPE intra-articular injection group could significantly improve the toe swelling of rats,reduce the expression of inflammatory factors and relieve the RA condition. However,the experimental results showed that Sin-NSSPE had a better therapeutic effect,and the stability of the dosage form was improved,which formed a drug reservoir,making the drug effect more stable. Conclusion The above results indicated that the prepared Sin-NSSPE had stable properties,and intra-articular injection of Sin-NSSPE had a good therapeutic effect on RA in rats.
作者
张筠昊
梁霄
白皓天
李娅兰
孙淑慧
张倩倩
杨婧
王锐
ZHANG Jun-hao;LIANG Xiao;BAI Hao-tian;LI Ya-lan;SUN Shu-hui;ZHANG Qian-qian;YANG Jing;WANG Rui(School of Pharmacy,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;College of Basic Medicine,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;Key Laboratory of Basic and Applied Research of Northern Medicine,Ministry of Education,Harbin 150040,China)
出处
《中草药》
CAS
CSCD
北大核心
2022年第20期6412-6422,共11页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(82074271)
国家自然科学基金资助项目(81603418)
黑龙江省属本科高校中央支持地方高校改革发展项目(2020YQ05)。
