College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wuya Collage of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Biomater Adv. 2022 Apr;135:212729. doi: 10.1016/j.bioadv.2022.212729. Epub 2022 Apr 22.
Multiple sclerosis is a chronic progressive demyelinating disease of the central nervous system. At present, systemic drug therapy for multiple sclerosis has limited efficacy and serious side effects. Everolimus, as a new generation of mTOR inhibitors, can effectively alleviate the inflammatory reaction of the central nervous system and offers a promising choice for the treatment of multiple sclerosis. However, due to the low oral bioavailability and narrow response window of oral everolimus, a new delivery system is urgently needed to overcome the above problems. In this study, we constructed a tip-concentrated microneedle patch as a transdermal delivery system of everolimus for the treatment of multiple sclerosis. Here, the drug was concentrated in the needle tips by the rational design, making it delivered completely into the skin. The therapeutic effect of everolimus-loaded microneedles was evaluated using the experimental autoimmune encephalomyelitis (EAE) model and further verified with neurological function scores and the histopathological results of the spinal cord. These results indicated that the tip-concentrated microneedle patch provided an effective, safe and simple method for the transdermal delivery of everolimus, thus providing a new treatment for multiple sclerosis.
多发性硬化症是一种中枢神经系统的慢性进行性脱髓鞘疾病。目前，多发性硬化症的全身药物治疗疗效有限，且具有严重的副作用。依维莫司作为新一代 mTOR 抑制剂，能有效缓解中枢神经系统的炎症反应，为多发性硬化症的治疗提供了有前景的选择。然而，由于口服依维莫司的口服生物利用度低和响应窗口狭窄，因此迫切需要一种新的给药系统来克服上述问题。在本研究中，我们构建了尖端集中型微针贴片作为依维莫司的透皮给药系统，用于治疗多发性硬化症。在这里，通过合理设计将药物集中在针尖，使药物完全递送到皮肤中。通过实验性自身免疫性脑脊髓炎（EAE）模型评估了载有依维莫司的微针的治疗效果，并通过脊髓的神经功能评分和组织病理学结果进一步验证。这些结果表明，尖端集中型微针贴片为依维莫司的透皮给药提供了一种有效、安全且简单的方法，为多发性硬化症的治疗提供了新的选择。
