Anhui University of Chinese Medicine, No.1 Qianjiang Street, Xinzhan Distinct, 230012, Hefei, Anhui, China.
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Biomed Pharmacother. 2019 Sep;117:108993. doi: 10.1016/j.biopha.2019.108993. Epub 2019 Jun 20.
The aim of this study was to investigate the release behaviors of sinomenine hydrochloride loaded via in situ hexagonal liquid crystal (ISH), and its potential to improve the local bioavailability in knee joints of sinomenine hydrochloride (SMH) after intra-articular administration. The ISH was prepared by a liquid precursor mixture containing phytantriol (PT), Vitamin E acetate (VEA), ethanol (ET), and water. The in vitro release profiles revealed a sustained release of SMH from the optimized ISH formula (PT/VEA/ET/water, 60.8:3.2:16.0:20.0, w/w/w/w), which was selected for the in vivo pharmacokinetics and preliminary pharmacodynamics studies. In both healthy and adjuvant-induced arthritis (AA) rats, the SMH loaded ISH showed significantly smaller SMH AUC in plasma (P < 0.01), and higher SMH concentration in synoviums (2˜168 h) than that of SMH solution, indicating that the ISH significantly reduced the leakage of SMH into systemic circulation. The t of SMH loaded ISH in the knee joints of AA rats, was longer (13.42 h) than that of healthy rats (1.34 h) (P < 0.05), most likely that in vivo drug release behavior of SMH loaded ISH was affected by the physiological environment of the joint. It was found that the SMH loaded ISH could benefit AA-rats by suppressing the level of IL-1β in comparison to SMH solutions. The results of the histopathology of knee joints in AA rats displayed that the SMH loaded ISH might be suitable for the development of treatment strategies for rheumatoid arthritis diseases.
本研究旨在考察盐酸青藤碱原位六方液晶（ISH）载药的释放行为，以及其在关节内给药后提高盐酸青藤碱（SMH）在膝关节局部生物利用度的潜力。ISH 由含有植物三醇（PT）、维生素 E 醋酸酯（VEA）、乙醇（ET）和水的液体前体混合物制备。体外释放曲线表明，从优化的 ISH 配方（PT/VEA/ET/水，60.8:3.2:16.0:20.0，w/w/w/w）中可以持续释放 SMH，因此选择该配方进行体内药代动力学和初步药效学研究。在健康和佐剂诱导关节炎（AA）大鼠中，SMH 负载 ISH 在血浆中的 SMH AUC 明显更小（P < 0.01），在滑膜中的 SMH 浓度（2~168 h）更高，表明 ISH 显著减少了 SMH 向全身循环的泄漏。AA 大鼠膝关节中 SMH 负载 ISH 的 t 1/2 较长（13.42 h），比健康大鼠（1.34 h）长（P < 0.05），这很可能是由于 ISH 载药在体内的药物释放行为受到关节生理环境的影响。与 SMH 溶液相比，发现 SMH 负载 ISH 可以通过抑制 IL-1β 的水平使 AA 大鼠受益。AA 大鼠膝关节组织病理学的结果显示，SMH 负载 ISH 可能适合开发类风湿关节炎疾病的治疗策略。
