Artemisinin emulgel ameliorates cartilage degradation in knee osteoarthritis: <i>in vitro</i> and <i>in vivo</i> studies

<b>Aim:</b> Laboratory scale-up of artemisinin-loaded emulgel (ART-emulgel) was carried out and characterized for therapeutic performance in osteoarthritis (OA). <b>Materials &amp; methods:</b> The solubility of ART in various oils, surfactants and co-surfactants were screened for construction of pseudo ternary phase diagram (TPD), followed by scale-up of artemisinin loaded nanoemulsion (ART-NE). ART-NE was amalgamated with Carbopol Ultrez 10-NF to prepare ART-emulgel that was later characterized <i>in vitro</i> and <i>in vivo</i> to analyze therapeutic efficacy in monosodium-iodoacetate (MIA) induced knee OA. <b>Results:</b> The droplet diameter of ART-NE was estimated to be 104.3 ± 2.593 nm with a polydispersity index of 0.245 ± 0.019 in addition to ζ-potential of 0.434 ± 0.028 mV. Steady-state flux and permeability coefficient for ART-emulgel were estimated to be 0.651 ± 0.031 µg.cm²/h and 0.245 ± 0.011 cm/h, respectively. ART-emulgel demonstrated 43.18% reduction in COX-2 level; 52.28% drop in IL-1β, and 88.78% alleviation of Tumor Necrosis Factor-α (TNF-α) level when compared with monosodium-iodoacetate induced OA rats. ART-emulgel and injectable ART (intra-articular; I.A) portrayed minor synovial erosion compared with blank and diclofenac emulgel. Histopathological evidences indicated restoration of cartilage integrity followed by reduction of OARSI scores in ART-emulgel when compared with disease control animals. <b>Conclusion:</b> ART-emulgel is a potential dosage form for translating into a clinically viable product for the management of OA. Artemisinin (ART) has shown critical role in the management of osteoarthritis ART-emulgel owing to submicron size demonstrated high dermal permeation by following the transappendageal pathway ART-emulgel reduces COX-2 expression in addition to TNF-α and IL-1β in experimental osteoarthritic rats. Histopathological analysis revealed restoration of cartilage integrity in ART-emulgel treated group**研究目的：** 开展青蒿素负载型乳凝胶（artemisinin-loaded emulgel, ART-emulgel）的实验室放大制备，并对其在骨关节炎（osteoarthritis, OA）中的治疗性能进行表征。 **材料与方法：** 筛选青蒿素（artemisinin, ART）在多种油相、表面活性剂及助表面活性剂中的溶解度，用于构建伪三元相图（pseudo ternary phase diagram, TPD），随后放大制备青蒿素负载型纳米乳（artemisinin loaded nanoemulsion, ART-NE）。将ART-NE与卡波姆Ultrez 10-NF（Carbopol Ultrez 10-NF）混合制备ART-emulgel，随后开展*体外*（in vitro）与*体内*（in vivo）表征，分析其在单碘乙酸钠（monosodium-iodoacetate, MIA）诱导的膝骨关节炎模型中的治疗效果。 **结果：** ART-NE的液滴粒径为104.3±2.593 nm，多分散指数为0.245±0.019，ζ电位为0.434±0.028 mV。ART-emulgel的稳态通透通量与通透系数分别为0.651±0.031 μg·cm⁻²·h⁻¹与0.245±0.011 cm·h⁻¹。与单碘乙酸钠诱导的骨关节炎模型大鼠相比，ART-emulgel可使COX-2水平降低43.18%、IL-1β水平下降52.28%，肿瘤坏死因子-α（Tumor Necrosis Factor-α, TNF-α）水平降低88.78%。与空白组与双氯芬酸乳凝胶组相比，ART-emulgel与注射用青蒿素（关节腔内给药；intra-articular, I.A）仅引发轻微滑膜侵蚀。组织病理学证据显示，与疾病对照组动物相比，ART-emulgel治疗组的软骨完整性得以恢复，且OARSI评分降低。 **结论：** ART-emulgel是一种具有转化潜力的剂型，有望开发为可用于骨关节炎临床治疗的可行产品。青蒿素（ART）在骨关节炎治疗中发挥关键作用；ART-emulgel因具有亚微米粒径，可通过经表皮附属器途径实现高效经皮渗透。ART-emulgel可降低实验性骨关节炎大鼠体内的COX-2、TNF-α与IL-1β表达水平。组织病理学分析显示，ART-emulgel治疗组的软骨完整性得以恢复。