Abstract：
Despite the fact that several rheumatoid arthritis treatments have been utilized, none of them achieved complete joint healing and has been accompanied by several side effects that compromise patient compliance. This study aims to provide an effective safe RA treatment with minimum side effects through the encapsulation of melatonin (MEL) in hyalurosomes and loading these hyalurosomes in collagen thermos-sensitive poloxamer 407 (PCO) hydrogels, followed by their intra-articular administration in AIA model rats. In vitro characterization of MEL-hyalurosomes and PCO hydrogel along with in vivo evaluation of the selected formulation were conducted. Particle size, PDI and EE % of the selected formulation were 71.5 nm, 0.09 and 90 %. TEM micrographs demonstrated that the particles had spherical shape with no aggregation signs. Loading PCO hydrogels with MEL-hyalurosomes did not cause significant changes in pH although it increased its viscosity and injection time. FTIR analysis showed that no interactions were noted among the delivery system components. In vivo results revealed the superior effect of MEL-hyalurosomes PCO hydrogel over MEL-PCO hydrogel and blank PCO hydrogels in improving joint healing, cartilage repair, pannus formation and cell infiltrations. Also, MEL-hyalurosomes PCO hydrogel group showed comparable levels of TNF-α, IL1, MDA, NRF2 and HO-1 with the negative control group. These findings highlight the MEL encapsulation role in augmenting its pharmacological effects along with the synergistic effect of hyaluronic acid in hyalurosomes and collagen in PCO hydrogel in promoting joint healing.
摘要：
尽管已经使用了几种类风湿性关节炎治疗方法，他们都没有实现完全的关节愈合，并伴随着一些损害患者依从性的副作用。这项研究旨在通过将褪黑激素（MEL）封装在透明体中，并将这些透明体加载到胶原蛋白热敏敏感的泊洛沙姆407（PCO）水凝胶中，提供有效的安全RA治疗，副作用最小。然后在AIA模型大鼠中进行关节内给药。进行MEL-透明体和PCO水凝胶的体外表征以及所选制剂的体内评估。粒度,所选配方的PDI和EE%为71.5nm，0.09和90%。TEM显微照片表明，颗粒具有球形，没有聚集迹象。将PCO水凝胶与MEL-透明体一起加载不会引起pH的显着变化，尽管它增加了粘度和注射时间。FTIR分析显示在递送系统组分之间没有观察到相互作用。体内实验结果揭示了MEL-透明体PCO水凝胶在改善关节愈合方面优于MEL-PCO水凝胶和空白PCO水凝胶。软骨修复,血管nu形成和细胞浸润。此外，MEL-hyalurosomesPCO水凝胶组显示出相当水平的TNF-α，IL1、MDA、NRF2和HO-1同阴性对照组。这些发现强调了MEL封装在增强其药理作用中的作用以及透明质酸在透明体中和PCO水凝胶中的胶原蛋白在促进关节愈合中的协同作用。
