Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Drug Des Devel Ther. 2020 Feb 28;14:921-931. doi: 10.2147/DDDT.S242493. eCollection 2020.
Intervertebral disc degeneration (IVDD) is the main cause of modern low back pain, leading to high societal economic costs. To find an effective medical treatment for this disease, oxymatrine liposomes (OMT-LIP) were prepared with the pH-gradient method.
Nucleus pulposus (NP) cells from Sprague-Dawley rats were used for the cell experiments. Kunming mice were used for in vivo imaging. LIP were employed to deliver OMT, and the particle size, ζ-potential, morphology, in vitro stability and in vitro release characteristics were evaluated. The OMT-LIP targeting effect was measured by in vivo imaging. Cell Counting Kit-8 assays were used to detect the cytotoxicity of OMT and OMT-LIP on NP cells. Therapeutic efficacy was measured by Western blot, real-time quantitative polymerase chain reaction, and apoptosis assays. Radiologic analysis was performed to evaluate the therapeutic effects in vivo.
Orthogonal test results revealed that the mass ratio of egg yolk phosphatidylcholine to cholesterol was the key factor to effectively trap OMT in LIP. Optimal OMT-LIP showed multivesicular structure with entrapment efficiency of 73.4 ± 4.1%, particle size of 178.1 ± 2.9 nm, and ζ-potential of -13.30 ± 2.34 mV. OMT-LIP manifested excellent stability in vitro and presented significantly longer sustained release compared to OMT solution in phosphate-buffered saline (pH 7.4). OMT-LIP conspicuously increased OMT accumulation in the degenerative disc, attenuated NP cell apoptosis, reduced the expression of matrix metalloproteinases 3/9 and interleukin-6, and decreased degradation of type II collagen. In in vivo study, X-ray demonstrated that OMT-LIP inhibited IVDD.
OMT-LIP may be a useful treatment to alleviate disc inflammation and IVDD.
椎间盘退变（IVDD）是现代腰痛的主要原因，导致了高昂的社会经济成本。为了找到这种疾病的有效治疗方法，采用 pH 梯度法制备氧化苦参碱脂质体（OMT-LIP）。
使用 Sprague-Dawley 大鼠的髓核（NP）细胞进行细胞实验。昆明小鼠用于体内成像。采用脂质体（LIP）递送 OMT，评估其粒径、ζ-电位、形态、体外稳定性和体外释放特性。通过体内成像测量 OMT-LIP 的靶向效果。使用细胞计数试剂盒-8 检测 OMT 和 OMT-LIP 对 NP 细胞的细胞毒性。通过 Western blot、实时定量聚合酶链反应和凋亡实验测量治疗效果。进行放射学分析以评估体内治疗效果。
正交试验结果表明，卵黄卵磷脂与胆固醇的质量比是有效包封 OMT 于脂质体中的关键因素。最佳 OMT-LIP 呈现多泡状结构，包封效率为 73.4±4.1%，粒径为 178.1±2.9nm，ζ-电位为-13.30±2.34mV。OMT-LIP 在体外表现出优异的稳定性，与磷酸盐缓冲盐水（pH7.4）中的 OMT 溶液相比，呈现出明显更长的持续释放。OMT-LIP 显著增加退变椎间盘内的 OMT 积累，减轻 NP 细胞凋亡，降低基质金属蛋白酶 3/9 和白细胞介素 6 的表达，并减少 II 型胶原的降解。在体内研究中，X 射线显示 OMT-LIP 抑制了 IVDD。
OMT-LIP 可能是一种缓解椎间盘炎症和 IVDD 的有效治疗方法。
