本研究介绍了一种重复建模的新方法,以模拟人类复发性痛风发作的病理过程。这种方法解决了痛风大鼠模型中存在的不稳定性问题,提供了对人体骨骼系统造成的损害复发性痛风发作的更准确的表示。开发了一种包封秋水仙碱和艾拉莫德乙醇制剂的可溶性纳米针系统。该系统旨在调节炎症细胞因子并抑制破骨细胞活性,从而治疗与复发性痛风相关的炎性疼痛和骨损伤。此外,全面评估微针的外观,形态学,机械性能,和穿透能力证实了它们穿透角质层的有效性。溶解测试和皮肤刺激评估表明这些微针快速溶解而不刺激皮肤。体外渗透研究表明,与传统的局部应用相比,通过这些微针的透皮药物递送更有效并且导致更低的药物损失。在动物模型中进行的体内药效学评估显示,当两种类型的微针一起使用时,显著的镇痛和抗炎作用。进一步分析,包括X射线成像,苏木精和伊红(H&E)染色,Safranin-O/快速绿色染色,抗酒石酸酸性磷酸酶染色,和破骨细胞的定量,证实了微针组合的骨保护作用。总之,这项研究的结果强调了这种新的治疗方法在复发性痛风的临床应用中的潜力。
This study introduces a novel approach of repetitive modeling to simulate the pathological process of recurrent gout attacks in humans. This methodology addresses the instability issues present in rat models of gout, providing a more accurate representation of the damage recurrent gout episodes inflict on human skeletal systems. A soluble nanoneedle system encapsulating colchicine and iguratimod ethosomal formulations was developed. This system aims to modulate inflammatory cytokines and inhibit osteoclast activity, thereby treating inflammatory pain and bone damage associated with recurrent gout. Additionally, a comprehensive evaluation of the microneedles\' appearance, morphology, mechanical properties, and penetration capability confirmed their effectiveness in penetrating the stratum corneum. Dissolution tests and skin irritation assessments demonstrated that these microneedles dissolve rapidly without irritating the skin. In vitro permeation studies indicated that transdermal drug delivery via these microneedles is more efficient and incurs lower drug loss compared to traditional topical applications. In vivo pharmacodynamic assessments conducted in animal models revealed significant analgesic and anti-inflammatory effects when both types of microneedles were used together. Further analyses, including X-ray imaging, hematoxylin and eosin (H&E) staining, Safranin-O/fast green staining, tartrate-resistant acid phosphatase staining, and quantification of osteoclasts, confirmed the bone-protective effects of the
microneedle combination. In conclusion, the findings of this research underscore the potential of this novel therapeutic approach for clinical application in the treatment of recurrent gout.